Cardiology

In elderly or low-weight patients with acute coronary syndrome (ACS), a reduced dose of prasugrel relative to a full-dose of ticagrelor is associated with lower numerical rates of ischemic events and bleeding events, according to a prespecified substudy of the ISAR-REACT 5 trial.

“The present study provides the strongest support for reduced-dose prasugrel as the standard for elderly and low-weight patients with ACS undergoing an invasive treatment strategy,” according to the senior author, Adnan Kastrati, MD, professor of cardiology and head of the Catheterization Laboratory at Deutsches Herzzentrum, Technical University of Munich.

The main results of ISAR-REACT 5, an open-label, head-to-head comparison of prasugrel and ticagrelor in patients with ACS, showed that the risk of the composite primary endpoint of death, myocardial infarction, or stroke 1 year after randomization was significantly higher for those on ticagrelor than prasugrel (hazard ratio, 1.39; P = .006). The bleeding risk on ticagrelor was also higher but not significantly different (5.4% vs. 4.8%; P = .46) (Schüpke S et al. N Engl J Med. 2019 Oct;381:1524-34).

In this substudy newly published in Annals of Internal Medicine, outcomes were compared in the 1,099 patients who were 75 years or older or weighed less than 60 kg. In this group, unlike those younger or weighing more, patients were randomized to receive a reduced maintenance dose of 5 mg of once-daily prasugrel (rather than 10 mg) or full dose ticagrelor (90 mg twice daily).

At 1 year, the low-dose prasugrel strategy relative to ticagrelor was associated with a lower rate of events (12.7% vs. 14.6%) and a lower rate of bleeding (8.1% vs. 10.6%), defined as Bleeding Academic Research Consortium (BARC) type 3-5 events.

Neither the 18% reduction for the efficacy endpoint (HR, 0.82; 95% CI 0.60-1.14) nor the 28% reduction in the bleeding endpoint (HR, 0.72; 95% CI 0.46-1.12) reached significance, but Dr. Kastrati reported that there was a significant “treatment effect-by-study-group interaction” for BARC 1-5 bleeding (P = .004) favoring prasugrel. This supports low-dose prasugrel as a strategy to prevent the excess bleeding risk previously observed with the standard 10-mg dose of prasugrel.

In other words, a reduced dose of prasugrel, compared with the standard dose of ticagrelor, in low-weight and elderly patients “is associated with maintained anti-ischemic efficacy while protecting these patients against the excess risk of bleeding,” he and his coinvestigators concluded.

Low-weight and older patients represented 27% of those enrolled in ISAR-REACT 5. When compared to the study population as a whole, the risk for both ischemic and bleeding events was at least twice as high, the authors of an accompanying editorial observed. They praised this effort to refine the optimal antiplatelet regimen in a very-high-risk ACS population.

“The current analysis suggests that the prasugrel dose reduction regimen for elderly or underweight patients with ACS is effective and safe,” according to the editorial coauthors, David Conen, MD, and P.J. Devereaux, MD, PhD, who are affiliated with the Population Health Research Institute, Hamilton, Ontario.

This substudy was underpowered to show superiority for the efficacy and safety outcomes in elderly and low-weight ACS patients, which makes these results “hypothesis generating,” but the authors believe that they provide the best available evidence for selecting antiplatelet therapy in this challenging subgroup. Although the exclusion of patients at very high risk of bleeding from ISAR-REACT 5 suggest findings might not be relevant to all elderly and low-weight individuals, the investigators believe the data do inform clinical practice.

“Our study is the first head-to-head randomized comparison of the reduced dose of prasugrel against standard dose of ticagrelor in elderly and low-weight patients,” said Dr. Kastrati in an interview. “Specifically designed studies for this subset of patients are very unlikely to be conducted in the future.”

Dr. Kastrati reported no potential conflicts of interest relevant to this study.

SOURCE: Menichelli M et al. Ann Intern Med. 2020 Jul 21. doi: 10.7326/M20-1806.

In elderly or low-weight patients with acute coronary syndrome (ACS), a reduced dose of prasugrel relative to a full-dose of ticagrelor is associated with lower numerical rates of ischemic events and bleeding events, according to a prespecified substudy of the ISAR-REACT 5 trial.

“The present study provides the strongest support for reduced-dose prasugrel as the standard for elderly and low-weight patients with ACS undergoing an invasive treatment strategy,” according to the senior author, Adnan Kastrati, MD, professor of cardiology and head of the Catheterization Laboratory at Deutsches Herzzentrum, Technical University of Munich.

The main results of ISAR-REACT 5, an open-label, head-to-head comparison of prasugrel and ticagrelor in patients with ACS, showed that the risk of the composite primary endpoint of death, myocardial infarction, or stroke 1 year after randomization was significantly higher for those on ticagrelor than prasugrel (hazard ratio, 1.39; P = .006). The bleeding risk on ticagrelor was also higher but not significantly different (5.4% vs. 4.8%; P = .46) (Schüpke S et al. N Engl J Med. 2019 Oct;381:1524-34).

In this substudy newly published in Annals of Internal Medicine, outcomes were compared in the 1,099 patients who were 75 years or older or weighed less than 60 kg. In this group, unlike those younger or weighing more, patients were randomized to receive a reduced maintenance dose of 5 mg of once-daily prasugrel (rather than 10 mg) or full dose ticagrelor (90 mg twice daily).

At 1 year, the low-dose prasugrel strategy relative to ticagrelor was associated with a lower rate of events (12.7% vs. 14.6%) and a lower rate of bleeding (8.1% vs. 10.6%), defined as Bleeding Academic Research Consortium (BARC) type 3-5 events.

Neither the 18% reduction for the efficacy endpoint (HR, 0.82; 95% CI 0.60-1.14) nor the 28% reduction in the bleeding endpoint (HR, 0.72; 95% CI 0.46-1.12) reached significance, but Dr. Kastrati reported that there was a significant “treatment effect-by-study-group interaction” for BARC 1-5 bleeding (P = .004) favoring prasugrel. This supports low-dose prasugrel as a strategy to prevent the excess bleeding risk previously observed with the standard 10-mg dose of prasugrel.

In other words, a reduced dose of prasugrel, compared with the standard dose of ticagrelor, in low-weight and elderly patients “is associated with maintained anti-ischemic efficacy while protecting these patients against the excess risk of bleeding,” he and his coinvestigators concluded.

Low-weight and older patients represented 27% of those enrolled in ISAR-REACT 5. When compared to the study population as a whole, the risk for both ischemic and bleeding events was at least twice as high, the authors of an accompanying editorial observed. They praised this effort to refine the optimal antiplatelet regimen in a very-high-risk ACS population.

“The current analysis suggests that the prasugrel dose reduction regimen for elderly or underweight patients with ACS is effective and safe,” according to the editorial coauthors, David Conen, MD, and P.J. Devereaux, MD, PhD, who are affiliated with the Population Health Research Institute, Hamilton, Ontario.

This substudy was underpowered to show superiority for the efficacy and safety outcomes in elderly and low-weight ACS patients, which makes these results “hypothesis generating,” but the authors believe that they provide the best available evidence for selecting antiplatelet therapy in this challenging subgroup. Although the exclusion of patients at very high risk of bleeding from ISAR-REACT 5 suggest findings might not be relevant to all elderly and low-weight individuals, the investigators believe the data do inform clinical practice.

“Our study is the first head-to-head randomized comparison of the reduced dose of prasugrel against standard dose of ticagrelor in elderly and low-weight patients,” said Dr. Kastrati in an interview. “Specifically designed studies for this subset of patients are very unlikely to be conducted in the future.”

Dr. Kastrati reported no potential conflicts of interest relevant to this study.

SOURCE: Menichelli M et al. Ann Intern Med. 2020 Jul 21. doi: 10.7326/M20-1806.

In elderly or low-weight patients with acute coronary syndrome (ACS), a reduced dose of prasugrel relative to a full-dose of ticagrelor is associated with lower numerical rates of ischemic events and bleeding events, according to a prespecified substudy of the ISAR-REACT 5 trial.

“The present study provides the strongest support for reduced-dose prasugrel as the standard for elderly and low-weight patients with ACS undergoing an invasive treatment strategy,” according to the senior author, Adnan Kastrati, MD, professor of cardiology and head of the Catheterization Laboratory at Deutsches Herzzentrum, Technical University of Munich.

The main results of ISAR-REACT 5, an open-label, head-to-head comparison of prasugrel and ticagrelor in patients with ACS, showed that the risk of the composite primary endpoint of death, myocardial infarction, or stroke 1 year after randomization was significantly higher for those on ticagrelor than prasugrel (hazard ratio, 1.39; P = .006). The bleeding risk on ticagrelor was also higher but not significantly different (5.4% vs. 4.8%; P = .46) (Schüpke S et al. N Engl J Med. 2019 Oct;381:1524-34).

In this substudy newly published in Annals of Internal Medicine, outcomes were compared in the 1,099 patients who were 75 years or older or weighed less than 60 kg. In this group, unlike those younger or weighing more, patients were randomized to receive a reduced maintenance dose of 5 mg of once-daily prasugrel (rather than 10 mg) or full dose ticagrelor (90 mg twice daily).

At 1 year, the low-dose prasugrel strategy relative to ticagrelor was associated with a lower rate of events (12.7% vs. 14.6%) and a lower rate of bleeding (8.1% vs. 10.6%), defined as Bleeding Academic Research Consortium (BARC) type 3-5 events.

Neither the 18% reduction for the efficacy endpoint (HR, 0.82; 95% CI 0.60-1.14) nor the 28% reduction in the bleeding endpoint (HR, 0.72; 95% CI 0.46-1.12) reached significance, but Dr. Kastrati reported that there was a significant “treatment effect-by-study-group interaction” for BARC 1-5 bleeding (P = .004) favoring prasugrel. This supports low-dose prasugrel as a strategy to prevent the excess bleeding risk previously observed with the standard 10-mg dose of prasugrel.

In other words, a reduced dose of prasugrel, compared with the standard dose of ticagrelor, in low-weight and elderly patients “is associated with maintained anti-ischemic efficacy while protecting these patients against the excess risk of bleeding,” he and his coinvestigators concluded.

Low-weight and older patients represented 27% of those enrolled in ISAR-REACT 5. When compared to the study population as a whole, the risk for both ischemic and bleeding events was at least twice as high, the authors of an accompanying editorial observed. They praised this effort to refine the optimal antiplatelet regimen in a very-high-risk ACS population.

“The current analysis suggests that the prasugrel dose reduction regimen for elderly or underweight patients with ACS is effective and safe,” according to the editorial coauthors, David Conen, MD, and P.J. Devereaux, MD, PhD, who are affiliated with the Population Health Research Institute, Hamilton, Ontario.

This substudy was underpowered to show superiority for the efficacy and safety outcomes in elderly and low-weight ACS patients, which makes these results “hypothesis generating,” but the authors believe that they provide the best available evidence for selecting antiplatelet therapy in this challenging subgroup. Although the exclusion of patients at very high risk of bleeding from ISAR-REACT 5 suggest findings might not be relevant to all elderly and low-weight individuals, the investigators believe the data do inform clinical practice.

“Our study is the first head-to-head randomized comparison of the reduced dose of prasugrel against standard dose of ticagrelor in elderly and low-weight patients,” said Dr. Kastrati in an interview. “Specifically designed studies for this subset of patients are very unlikely to be conducted in the future.”

Dr. Kastrati reported no potential conflicts of interest relevant to this study.

SOURCE: Menichelli M et al. Ann Intern Med. 2020 Jul 21. doi: 10.7326/M20-1806.

Using point-of-care ultrasound, internists can reduce the number of tests performed in a hospital without affecting mortality, researchers say.

“It’s a safe and very useful tool,” Marco Barchiesi, MD, an internal medicine resident at Luigi Sacco Hospital in Milan, said in an interview. “We had a great reduction in chest x-rays because of the use of ultrasound.”

The finding addresses concerns that ultrasound used in primary care could consume more health care resources or put patients at risk.

Dr. Barchiesi and colleagues published their findings July 20 in the European Journal of Internal Medicine.

Point-of-care ultrasound has become increasingly common as miniaturization of devices has made them more portable. The approach has caught on particularly in emergency departments where quick decisions are of the essence.

Its use in internal medicine has been more controversial, with concerns raised that improperly trained practitioners may miss diagnoses or refer patients for unnecessary tests as a result of uncertainty about their findings.

To measure the effect of point-of-care ultrasound in an internal medicine hospital ward, Dr. Barchiesi and colleagues alternated months when point-of-care ultrasound was allowed with months when it was not allowed, for a total of 4 months each, on an internal medicine unit. They allowed the ultrasound to be used for invasive procedures and excluded patients whose critical condition made point-of-care ultrasound crucial.

The researchers analyzed data on 263 patients in the “on” months when point-of-care ultrasound was used, and 255 in the “off” months when it wasn’t used. The two groups were well balanced in age, sex, comorbidity, and clinical impairment.

During the on months, the internists ordered 113 diagnostic tests (0.43 per patient). During the off months they ordered 329 tests (1.29 per patient).

The odds of being referred for a chest x-ray were 87% less in the “on” months, compared with the off months, a statistically significant finding (P < .001). The risk for a chest CT scan and abdominal ultrasound were also reduced during the on months, but the risk for an abdominal CT was increased.

Nineteen patients died during the o” months and 10 during the off months, a difference that was not statistically significant (P = .15). The median length of stay in the hospital was almost the same for the two groups: 9 days for the on months and 9 days for the off months. The difference was also not statistically significant (P = .094).

Point-of-care ultrasound is particularly accurate in identifying cardiac abnormalities and pleural fluid and pneumonia, and it can be used effectively for monitoring heart conditions, the researchers wrote. This could explain the reduction in chest x-rays and CT scans.

On the other hand, ultrasound cannot address such questions as staging in an abdominal malignancy, and unexpected findings are more common with abdominal than chest ultrasound. This could explain why the point-of-care ultrasound did not reduce the use of abdominal CT, the researchers speculated.

They acknowledged that the patients in their sample had an average age of 81 years, raising questions about how well their data could be applied to a younger population. And they noted that they used point-of-care ultrasound frequently, so they were particularly adept with it. “We use it almost every day in our clinical practice,” said Dr. Barchiesi.

Those factors may have played a key role in the success of point-of-care ultrasound in this study, said Michael Wagner, MD, an assistant professor of medicine at the University of South Carolina, Greenville, who has helped colleagues incorporate ultrasound into their practices.

Elderly patients often present with multiple comorbidities and atypical signs and symptoms, he said. “Sometimes they can be very confusing as to the underlying clinical picture. Ultrasound is being used frequently to better assess these complicated patients.”

Dr. Wagner said extensive training is required to use point-of-care ultrasound accurately.

Dr. Barchiesi also acknowledged that the devices used in this study were large portable machines, not the simpler and less expensive hand-held versions that are also available for similar purposes.

Point-of-care ultrasound is a promising innovation, said Thomas Melgar, MD, a professor of medicine at Western Michigan University, Kalamazoo. “The advantage is that the exam is being done by someone who knows the patient and specifically what they’re looking for. It’s done at the bedside so you don’t have to move the patient.”

The study could help address opposition to internal medicine residents being trained in the technique, he said, adding that “I think it’s very exciting.”

The study was partially supported by Philips, which provided the ultrasound devices. Dr. Barchiesi, Dr. Melgar, and Dr. Wagner disclosed no relevant financial relationships.

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

Using point-of-care ultrasound, internists can reduce the number of tests performed in a hospital without affecting mortality, researchers say.

“It’s a safe and very useful tool,” Marco Barchiesi, MD, an internal medicine resident at Luigi Sacco Hospital in Milan, said in an interview. “We had a great reduction in chest x-rays because of the use of ultrasound.”

The finding addresses concerns that ultrasound used in primary care could consume more health care resources or put patients at risk.

Dr. Barchiesi and colleagues published their findings July 20 in the European Journal of Internal Medicine.

Point-of-care ultrasound has become increasingly common as miniaturization of devices has made them more portable. The approach has caught on particularly in emergency departments where quick decisions are of the essence.

Its use in internal medicine has been more controversial, with concerns raised that improperly trained practitioners may miss diagnoses or refer patients for unnecessary tests as a result of uncertainty about their findings.

To measure the effect of point-of-care ultrasound in an internal medicine hospital ward, Dr. Barchiesi and colleagues alternated months when point-of-care ultrasound was allowed with months when it was not allowed, for a total of 4 months each, on an internal medicine unit. They allowed the ultrasound to be used for invasive procedures and excluded patients whose critical condition made point-of-care ultrasound crucial.

The researchers analyzed data on 263 patients in the “on” months when point-of-care ultrasound was used, and 255 in the “off” months when it wasn’t used. The two groups were well balanced in age, sex, comorbidity, and clinical impairment.

During the on months, the internists ordered 113 diagnostic tests (0.43 per patient). During the off months they ordered 329 tests (1.29 per patient).

The odds of being referred for a chest x-ray were 87% less in the “on” months, compared with the off months, a statistically significant finding (P < .001). The risk for a chest CT scan and abdominal ultrasound were also reduced during the on months, but the risk for an abdominal CT was increased.

Nineteen patients died during the o” months and 10 during the off months, a difference that was not statistically significant (P = .15). The median length of stay in the hospital was almost the same for the two groups: 9 days for the on months and 9 days for the off months. The difference was also not statistically significant (P = .094).

Point-of-care ultrasound is particularly accurate in identifying cardiac abnormalities and pleural fluid and pneumonia, and it can be used effectively for monitoring heart conditions, the researchers wrote. This could explain the reduction in chest x-rays and CT scans.

On the other hand, ultrasound cannot address such questions as staging in an abdominal malignancy, and unexpected findings are more common with abdominal than chest ultrasound. This could explain why the point-of-care ultrasound did not reduce the use of abdominal CT, the researchers speculated.

They acknowledged that the patients in their sample had an average age of 81 years, raising questions about how well their data could be applied to a younger population. And they noted that they used point-of-care ultrasound frequently, so they were particularly adept with it. “We use it almost every day in our clinical practice,” said Dr. Barchiesi.

Those factors may have played a key role in the success of point-of-care ultrasound in this study, said Michael Wagner, MD, an assistant professor of medicine at the University of South Carolina, Greenville, who has helped colleagues incorporate ultrasound into their practices.

Elderly patients often present with multiple comorbidities and atypical signs and symptoms, he said. “Sometimes they can be very confusing as to the underlying clinical picture. Ultrasound is being used frequently to better assess these complicated patients.”

Dr. Wagner said extensive training is required to use point-of-care ultrasound accurately.

Dr. Barchiesi also acknowledged that the devices used in this study were large portable machines, not the simpler and less expensive hand-held versions that are also available for similar purposes.

Point-of-care ultrasound is a promising innovation, said Thomas Melgar, MD, a professor of medicine at Western Michigan University, Kalamazoo. “The advantage is that the exam is being done by someone who knows the patient and specifically what they’re looking for. It’s done at the bedside so you don’t have to move the patient.”

The study could help address opposition to internal medicine residents being trained in the technique, he said, adding that “I think it’s very exciting.”

The study was partially supported by Philips, which provided the ultrasound devices. Dr. Barchiesi, Dr. Melgar, and Dr. Wagner disclosed no relevant financial relationships.

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

Using point-of-care ultrasound, internists can reduce the number of tests performed in a hospital without affecting mortality, researchers say.

“It’s a safe and very useful tool,” Marco Barchiesi, MD, an internal medicine resident at Luigi Sacco Hospital in Milan, said in an interview. “We had a great reduction in chest x-rays because of the use of ultrasound.”

The finding addresses concerns that ultrasound used in primary care could consume more health care resources or put patients at risk.

Dr. Barchiesi and colleagues published their findings July 20 in the European Journal of Internal Medicine.

Point-of-care ultrasound has become increasingly common as miniaturization of devices has made them more portable. The approach has caught on particularly in emergency departments where quick decisions are of the essence.

Its use in internal medicine has been more controversial, with concerns raised that improperly trained practitioners may miss diagnoses or refer patients for unnecessary tests as a result of uncertainty about their findings.

To measure the effect of point-of-care ultrasound in an internal medicine hospital ward, Dr. Barchiesi and colleagues alternated months when point-of-care ultrasound was allowed with months when it was not allowed, for a total of 4 months each, on an internal medicine unit. They allowed the ultrasound to be used for invasive procedures and excluded patients whose critical condition made point-of-care ultrasound crucial.

The researchers analyzed data on 263 patients in the “on” months when point-of-care ultrasound was used, and 255 in the “off” months when it wasn’t used. The two groups were well balanced in age, sex, comorbidity, and clinical impairment.

During the on months, the internists ordered 113 diagnostic tests (0.43 per patient). During the off months they ordered 329 tests (1.29 per patient).

The odds of being referred for a chest x-ray were 87% less in the “on” months, compared with the off months, a statistically significant finding (P < .001). The risk for a chest CT scan and abdominal ultrasound were also reduced during the on months, but the risk for an abdominal CT was increased.

Nineteen patients died during the o” months and 10 during the off months, a difference that was not statistically significant (P = .15). The median length of stay in the hospital was almost the same for the two groups: 9 days for the on months and 9 days for the off months. The difference was also not statistically significant (P = .094).

Point-of-care ultrasound is particularly accurate in identifying cardiac abnormalities and pleural fluid and pneumonia, and it can be used effectively for monitoring heart conditions, the researchers wrote. This could explain the reduction in chest x-rays and CT scans.

On the other hand, ultrasound cannot address such questions as staging in an abdominal malignancy, and unexpected findings are more common with abdominal than chest ultrasound. This could explain why the point-of-care ultrasound did not reduce the use of abdominal CT, the researchers speculated.

They acknowledged that the patients in their sample had an average age of 81 years, raising questions about how well their data could be applied to a younger population. And they noted that they used point-of-care ultrasound frequently, so they were particularly adept with it. “We use it almost every day in our clinical practice,” said Dr. Barchiesi.

Those factors may have played a key role in the success of point-of-care ultrasound in this study, said Michael Wagner, MD, an assistant professor of medicine at the University of South Carolina, Greenville, who has helped colleagues incorporate ultrasound into their practices.

Elderly patients often present with multiple comorbidities and atypical signs and symptoms, he said. “Sometimes they can be very confusing as to the underlying clinical picture. Ultrasound is being used frequently to better assess these complicated patients.”

Dr. Wagner said extensive training is required to use point-of-care ultrasound accurately.

Dr. Barchiesi also acknowledged that the devices used in this study were large portable machines, not the simpler and less expensive hand-held versions that are also available for similar purposes.

Point-of-care ultrasound is a promising innovation, said Thomas Melgar, MD, a professor of medicine at Western Michigan University, Kalamazoo. “The advantage is that the exam is being done by someone who knows the patient and specifically what they’re looking for. It’s done at the bedside so you don’t have to move the patient.”

The study could help address opposition to internal medicine residents being trained in the technique, he said, adding that “I think it’s very exciting.”

The study was partially supported by Philips, which provided the ultrasound devices. Dr. Barchiesi, Dr. Melgar, and Dr. Wagner disclosed no relevant financial relationships.

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

Patients on oral anticoagulants who experience a bleeding event may be able to discontinue therapy if certain circumstances apply, according to updated guidance from the American College of Cardiology.

The emergence of direct-acting oral anticoagulants (DOACs) to prevent venous thromboembolism and the introduction of new reversal strategies for factor Xa inhibitors prompted the creation of an Expert Consensus Decision Pathway to update the version from 2017, according to the ACC. Expert consensus decision pathways (ECDPs) are a component of the solution sets issued by the ACC to “address key questions facing care teams and attempt to provide practical guidance to be applied at the point of care.”

In an ECDP published in the Journal of the American College of Cardiology, the writing committee members developed treatment algorithms for managing bleeding in patients on DOACs and vitamin K antagonists (VKAs).

Bleeding was classified as major or nonmajor, with major defined as “bleeding that is associated with hemodynamic compromise, occurs in an anatomically critical site, requires transfusion of at least 2 units of packed red blood cells [RBCs]), or results in a hemoglobin drop greater than 2 g/dL. All other types of bleeding were classified as nonmajor.

The document includes a graphic algorithm for assessing bleed severity and managing major versus nonmajor bleeding, and a separate graphic describes considerations for reversal and use of hemostatic agents according to whether the patient is taking a VKA (warfarin and other coumarins), a direct thrombin inhibitor (dabigatran), the factor Xa inhibitors apixaban and rivaroxaban, or the factor Xa inhibitors betrixaban and edoxaban.

Another algorithm outlines whether to discontinue, delay, or restart anticoagulation. Considerations for restarting anticoagulation include whether the patient is pregnant, awaiting an invasive procedure, not able to receive medication by mouth, has a high risk of rebleeding, or is being bridged back to a vitamin K antagonist with high thrombotic risk.

In most cases of GI bleeding, for example, current data support restarting oral anticoagulants once hemostasis is achieved, but patients who experience intracranial hemorrhage should delay restarting any anticoagulation for at least 4 weeks if they are without high thrombotic risk, according to the document.

The report also recommends clinician-patient discussion before resuming anticoagulation, ideally with time allowed for patients to develop questions. Discussions should include the signs of bleeding, assessment of risk for a thromboembolic event, and the benefits of anticoagulation.

“The proliferation of oral anticoagulants (warfarin and DOACs) and growing indications for their use prompted the need for guidance on the management of these drugs,” said Gordon F. Tomaselli, MD, chair of the writing committee, in an interview. “This document provides guidance on management at the time of a bleeding complication. This includes acute management, starting and stopping drugs, and use of reversal agents,” he said. “This of course will be a dynamic document as the list of these drugs and their antidotes expand,” he noted.  

“The biggest change from the previous guidelines are twofold: an update on laboratory assessment to monitor drug levels and use of reversal agents,” while the acute management strategies have otherwise remained similar to previous documents, said Dr. Tomaselli.

Dr. Tomaselli said that he was not surprised by the biological aspects of recent research while developing the statement. However, “the extent of the use of multiple anticoagulants and antiplatelet agents was a bit surprising and complicates therapy with each of the agents,” he noted.

The way the pathways are presented may make them challenging to follow in clinical practice, said Dr. Tomaselli. “The pathways are described linearly and in practice often many things have to happen at once,” he said. “The other main issue may be limitations in the availability of some of the newer reversal agents,” he added.

“The complication of bleeding is difficult to avoid,” said Dr. Tomaselli, and for future research, “the focus needs to continue to refine the indications for anticoagulation and appropriate use with other drugs that predispose to bleeding. We also need better methods and testing to monitor drugs levels and the effect on coagulation,” he said.

In accordance with the ACC Solution Set Oversight Committee, the writing committee members, including Dr. Tomaselli, had no relevant relationships with industry to disclose.

SOURCE: Tomaselli GF et al. J Am Coll Cardiol. 2020. doi: 10.1016/j.jacc.2020.04.053.

Patients on oral anticoagulants who experience a bleeding event may be able to discontinue therapy if certain circumstances apply, according to updated guidance from the American College of Cardiology.

The emergence of direct-acting oral anticoagulants (DOACs) to prevent venous thromboembolism and the introduction of new reversal strategies for factor Xa inhibitors prompted the creation of an Expert Consensus Decision Pathway to update the version from 2017, according to the ACC. Expert consensus decision pathways (ECDPs) are a component of the solution sets issued by the ACC to “address key questions facing care teams and attempt to provide practical guidance to be applied at the point of care.”

In an ECDP published in the Journal of the American College of Cardiology, the writing committee members developed treatment algorithms for managing bleeding in patients on DOACs and vitamin K antagonists (VKAs).

Bleeding was classified as major or nonmajor, with major defined as “bleeding that is associated with hemodynamic compromise, occurs in an anatomically critical site, requires transfusion of at least 2 units of packed red blood cells [RBCs]), or results in a hemoglobin drop greater than 2 g/dL. All other types of bleeding were classified as nonmajor.

The document includes a graphic algorithm for assessing bleed severity and managing major versus nonmajor bleeding, and a separate graphic describes considerations for reversal and use of hemostatic agents according to whether the patient is taking a VKA (warfarin and other coumarins), a direct thrombin inhibitor (dabigatran), the factor Xa inhibitors apixaban and rivaroxaban, or the factor Xa inhibitors betrixaban and edoxaban.

Another algorithm outlines whether to discontinue, delay, or restart anticoagulation. Considerations for restarting anticoagulation include whether the patient is pregnant, awaiting an invasive procedure, not able to receive medication by mouth, has a high risk of rebleeding, or is being bridged back to a vitamin K antagonist with high thrombotic risk.

In most cases of GI bleeding, for example, current data support restarting oral anticoagulants once hemostasis is achieved, but patients who experience intracranial hemorrhage should delay restarting any anticoagulation for at least 4 weeks if they are without high thrombotic risk, according to the document.

The report also recommends clinician-patient discussion before resuming anticoagulation, ideally with time allowed for patients to develop questions. Discussions should include the signs of bleeding, assessment of risk for a thromboembolic event, and the benefits of anticoagulation.

“The proliferation of oral anticoagulants (warfarin and DOACs) and growing indications for their use prompted the need for guidance on the management of these drugs,” said Gordon F. Tomaselli, MD, chair of the writing committee, in an interview. “This document provides guidance on management at the time of a bleeding complication. This includes acute management, starting and stopping drugs, and use of reversal agents,” he said. “This of course will be a dynamic document as the list of these drugs and their antidotes expand,” he noted.  

“The biggest change from the previous guidelines are twofold: an update on laboratory assessment to monitor drug levels and use of reversal agents,” while the acute management strategies have otherwise remained similar to previous documents, said Dr. Tomaselli.

Dr. Tomaselli said that he was not surprised by the biological aspects of recent research while developing the statement. However, “the extent of the use of multiple anticoagulants and antiplatelet agents was a bit surprising and complicates therapy with each of the agents,” he noted.

The way the pathways are presented may make them challenging to follow in clinical practice, said Dr. Tomaselli. “The pathways are described linearly and in practice often many things have to happen at once,” he said. “The other main issue may be limitations in the availability of some of the newer reversal agents,” he added.

“The complication of bleeding is difficult to avoid,” said Dr. Tomaselli, and for future research, “the focus needs to continue to refine the indications for anticoagulation and appropriate use with other drugs that predispose to bleeding. We also need better methods and testing to monitor drugs levels and the effect on coagulation,” he said.

In accordance with the ACC Solution Set Oversight Committee, the writing committee members, including Dr. Tomaselli, had no relevant relationships with industry to disclose.

SOURCE: Tomaselli GF et al. J Am Coll Cardiol. 2020. doi: 10.1016/j.jacc.2020.04.053.

Patients on oral anticoagulants who experience a bleeding event may be able to discontinue therapy if certain circumstances apply, according to updated guidance from the American College of Cardiology.

The emergence of direct-acting oral anticoagulants (DOACs) to prevent venous thromboembolism and the introduction of new reversal strategies for factor Xa inhibitors prompted the creation of an Expert Consensus Decision Pathway to update the version from 2017, according to the ACC. Expert consensus decision pathways (ECDPs) are a component of the solution sets issued by the ACC to “address key questions facing care teams and attempt to provide practical guidance to be applied at the point of care.”

In an ECDP published in the Journal of the American College of Cardiology, the writing committee members developed treatment algorithms for managing bleeding in patients on DOACs and vitamin K antagonists (VKAs).

Bleeding was classified as major or nonmajor, with major defined as “bleeding that is associated with hemodynamic compromise, occurs in an anatomically critical site, requires transfusion of at least 2 units of packed red blood cells [RBCs]), or results in a hemoglobin drop greater than 2 g/dL. All other types of bleeding were classified as nonmajor.

The document includes a graphic algorithm for assessing bleed severity and managing major versus nonmajor bleeding, and a separate graphic describes considerations for reversal and use of hemostatic agents according to whether the patient is taking a VKA (warfarin and other coumarins), a direct thrombin inhibitor (dabigatran), the factor Xa inhibitors apixaban and rivaroxaban, or the factor Xa inhibitors betrixaban and edoxaban.

Another algorithm outlines whether to discontinue, delay, or restart anticoagulation. Considerations for restarting anticoagulation include whether the patient is pregnant, awaiting an invasive procedure, not able to receive medication by mouth, has a high risk of rebleeding, or is being bridged back to a vitamin K antagonist with high thrombotic risk.

In most cases of GI bleeding, for example, current data support restarting oral anticoagulants once hemostasis is achieved, but patients who experience intracranial hemorrhage should delay restarting any anticoagulation for at least 4 weeks if they are without high thrombotic risk, according to the document.

The report also recommends clinician-patient discussion before resuming anticoagulation, ideally with time allowed for patients to develop questions. Discussions should include the signs of bleeding, assessment of risk for a thromboembolic event, and the benefits of anticoagulation.

“The proliferation of oral anticoagulants (warfarin and DOACs) and growing indications for their use prompted the need for guidance on the management of these drugs,” said Gordon F. Tomaselli, MD, chair of the writing committee, in an interview. “This document provides guidance on management at the time of a bleeding complication. This includes acute management, starting and stopping drugs, and use of reversal agents,” he said. “This of course will be a dynamic document as the list of these drugs and their antidotes expand,” he noted.  

“The biggest change from the previous guidelines are twofold: an update on laboratory assessment to monitor drug levels and use of reversal agents,” while the acute management strategies have otherwise remained similar to previous documents, said Dr. Tomaselli.

Dr. Tomaselli said that he was not surprised by the biological aspects of recent research while developing the statement. However, “the extent of the use of multiple anticoagulants and antiplatelet agents was a bit surprising and complicates therapy with each of the agents,” he noted.

The way the pathways are presented may make them challenging to follow in clinical practice, said Dr. Tomaselli. “The pathways are described linearly and in practice often many things have to happen at once,” he said. “The other main issue may be limitations in the availability of some of the newer reversal agents,” he added.

“The complication of bleeding is difficult to avoid,” said Dr. Tomaselli, and for future research, “the focus needs to continue to refine the indications for anticoagulation and appropriate use with other drugs that predispose to bleeding. We also need better methods and testing to monitor drugs levels and the effect on coagulation,” he said.

In accordance with the ACC Solution Set Oversight Committee, the writing committee members, including Dr. Tomaselli, had no relevant relationships with industry to disclose.

SOURCE: Tomaselli GF et al. J Am Coll Cardiol. 2020. doi: 10.1016/j.jacc.2020.04.053.

The combination of ticagrelor and aspirin is superior to aspirin alone in reducing the risk for secondary stroke, transient ischemic attack (TIA), and death, new data show. However, severe bleeding was more common in the ticagrelor/aspirin group than in the aspirin-only group.

“We found that ticagrelor plus aspirin reduced the risk of stroke or death, compared to aspirin alone in patients presenting acutely with stroke or TIA,” reported lead author S. Claiborne Johnston, MD, PhD, dean and vice president for medical affairs, Dell Medical School, the University of Texas, Austin.

Although the combination also increased the risk for major hemorrhage, that increase was small and would not overwhelm the benefit, he said.

The study was published online July 16 in The New England Journal of Medicine.
 

Attractive properties

“Lots of patients have stroke in the days to weeks after first presenting with a stroke or TIA,” said Dr. Johnston, who is also the Frank and Charmaine Denius Distinguished Dean’s Chair at Dell Medical School. “Aspirin has been the standard of care but is only partially effective. Clopidogrel plus aspirin is another option that has recently been proven, [but] ticagrelor has attractive properties as an antiplatelet agent and works synergistically with aspirin,” he added.

Ticagrelor is a direct-acting antiplatelet agent that does not depend on metabolic activation and that “reversibly binds” and inhibits the P2Y12 receptor on platelets. Previous research has evaluated clopidogrel and aspirin for the secondary prevention of ischemic stroke or TIA. In an earlier trial, ticagrelor was no better than aspirin in preventing these subsequent events. However, the investigators noted that the combination of the two drugs has not been well studied.

The randomized, placebo-controlled, double-blind trial involved 11,016 patients at 414 sites in 28 countries. Patients who had experienced mild to moderate acute noncardioembolic ischemic stroke (mean age, 65 years; 39% women; roughly 54% White) were randomly assigned to receive either ticagrelor plus aspirin (n = 5,523) or aspirin alone (n = 5,493) for 30 days. Of these patients, 91% had sustained a stroke, and 9% had sustained a TIA.

Thirty days was chosen as the treatment period because the risk for subsequent stroke tends to occur mainly in the first month after an acute ischemic stroke or TIA. The primary outcome was “a composite of stroke or death in a time-to-first-event analysis from randomization to 30 days of follow-up.” For the study, “stroke” encompassed ischemic, hemorrhagic, or stroke of undetermined type, and “death” included deaths of all causes. Secondary outcomes included first subsequent ischemic stroke and disability (defined as a score of >1 on the Rankin Scale).

Almost all patients (99.5%) were taking aspirin during the treatment period, and most were also taking an antihypertensive and a statin (74% and 83%, respectively).

Patients in the ticagrelor/aspirin group had fewer primary-outcome events in comparison with those in the aspirin-only group (303 patients [5.5%] vs. 362 patients [6.6%]; hazard ratio, 0.83; 95% confidence interval, 0.71-0.96; P = 0.02). Incidence of subsequent ischemic stroke were similarly lower in the ticagrelor/aspirin group in comparison with the aspirin-only group (276 patients [5.0%] vs. 345 patients [6.3%]; HR, 0.79; 95% CI, 0.68-0.93; P = .004).

On the other hand, there was no significant difference between the groups in the incidence of overall disability (23.8% of the patients in the ticagrelor/aspirin group and in 24.1% of the patients in the aspirin group; odds ratio, 0.98; 95% CI, 0.89-1.07; P = .61).

There were differences between the groups in severe bleeding, which occurred in 28 patients (0.5%) in the ticagrelor/aspirin group and in seven patients (0.15) in the ticagrelor group (HR, 3.99; 95% CI, 1.74-9.14; P = .001). Moreover, more patients in the ticagrelor/aspirin group experienced a composite of intracranial hemorrhage or fatal bleeding compared with the aspirin-only group (0.4% vs 0.1%). Fatal bleeding occurred in 0.2% of patients in the ticagrelor/aspirin group versus 0.1% of patients in the aspirin group. More patients in the ticagrelor-aspirin group permanently discontinued the treatment because of bleeding than in the aspirin-only group (2.8% vs. 0.6%).

“The benefit from treatment with ticagrelor/aspirin, as compared with aspirin alone, would be expected to result in a number needed to treat of 92 to prevent one primary outcome event, and a number needed to harm of 263 for severe bleeding,” the authors noted.
 

Risks versus benefits

Commenting on the study, Konark Malhotra, MD, a vascular neurologist at Allegheny Health Network, Pittsburgh, noted that ticagrelor is an antiplatelet medication “that adds to the armamentarium of stroke neurologists for the treatment of mild acute ischemic or high-risk TIA patients.” Dr. Malhotra, who was not involved with the study, added that the “combined use of ticagrelor and aspirin is effective in the reduction of ischemic events, however, at the expense of increased risk of bleeding events.”

In an accompanying editorial, Peter Rothwell, MD, PhD, of the Wolfson Center for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences at the University of Oxford (England) who was not involved with the study, suggested that the “bleeding risk associated with ticagrelor and aspirin might exceed the benefit among lower-risk patients who make up the majority in practice, and so the results should not be overgeneralized.” Moreover, “regardless of which combination of antiplatelet therapy is favored for the high-risk minority, all patients should receive aspirin immediately after TIA, unless aspirin is contraindicated.”

He noted that “too many patients are sent home from emergency departments without this simple treatment that substantially reduces the risk and severity of early recurrent stroke.”

The study was supported by AstraZeneca. Dr. Johnston has received a grant from AstraZeneca and nonfinancial support from SANOFI. Dr. Rothwell has received personal fees from Bayer and BMS. Dr. Malhotra has disclosed no relevant financial relationships.

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

The combination of ticagrelor and aspirin is superior to aspirin alone in reducing the risk for secondary stroke, transient ischemic attack (TIA), and death, new data show. However, severe bleeding was more common in the ticagrelor/aspirin group than in the aspirin-only group.

“We found that ticagrelor plus aspirin reduced the risk of stroke or death, compared to aspirin alone in patients presenting acutely with stroke or TIA,” reported lead author S. Claiborne Johnston, MD, PhD, dean and vice president for medical affairs, Dell Medical School, the University of Texas, Austin.

Although the combination also increased the risk for major hemorrhage, that increase was small and would not overwhelm the benefit, he said.

The study was published online July 16 in The New England Journal of Medicine.
 

Attractive properties

“Lots of patients have stroke in the days to weeks after first presenting with a stroke or TIA,” said Dr. Johnston, who is also the Frank and Charmaine Denius Distinguished Dean’s Chair at Dell Medical School. “Aspirin has been the standard of care but is only partially effective. Clopidogrel plus aspirin is another option that has recently been proven, [but] ticagrelor has attractive properties as an antiplatelet agent and works synergistically with aspirin,” he added.

Ticagrelor is a direct-acting antiplatelet agent that does not depend on metabolic activation and that “reversibly binds” and inhibits the P2Y12 receptor on platelets. Previous research has evaluated clopidogrel and aspirin for the secondary prevention of ischemic stroke or TIA. In an earlier trial, ticagrelor was no better than aspirin in preventing these subsequent events. However, the investigators noted that the combination of the two drugs has not been well studied.

The randomized, placebo-controlled, double-blind trial involved 11,016 patients at 414 sites in 28 countries. Patients who had experienced mild to moderate acute noncardioembolic ischemic stroke (mean age, 65 years; 39% women; roughly 54% White) were randomly assigned to receive either ticagrelor plus aspirin (n = 5,523) or aspirin alone (n = 5,493) for 30 days. Of these patients, 91% had sustained a stroke, and 9% had sustained a TIA.

Thirty days was chosen as the treatment period because the risk for subsequent stroke tends to occur mainly in the first month after an acute ischemic stroke or TIA. The primary outcome was “a composite of stroke or death in a time-to-first-event analysis from randomization to 30 days of follow-up.” For the study, “stroke” encompassed ischemic, hemorrhagic, or stroke of undetermined type, and “death” included deaths of all causes. Secondary outcomes included first subsequent ischemic stroke and disability (defined as a score of >1 on the Rankin Scale).

Almost all patients (99.5%) were taking aspirin during the treatment period, and most were also taking an antihypertensive and a statin (74% and 83%, respectively).

Patients in the ticagrelor/aspirin group had fewer primary-outcome events in comparison with those in the aspirin-only group (303 patients [5.5%] vs. 362 patients [6.6%]; hazard ratio, 0.83; 95% confidence interval, 0.71-0.96; P = 0.02). Incidence of subsequent ischemic stroke were similarly lower in the ticagrelor/aspirin group in comparison with the aspirin-only group (276 patients [5.0%] vs. 345 patients [6.3%]; HR, 0.79; 95% CI, 0.68-0.93; P = .004).

On the other hand, there was no significant difference between the groups in the incidence of overall disability (23.8% of the patients in the ticagrelor/aspirin group and in 24.1% of the patients in the aspirin group; odds ratio, 0.98; 95% CI, 0.89-1.07; P = .61).

There were differences between the groups in severe bleeding, which occurred in 28 patients (0.5%) in the ticagrelor/aspirin group and in seven patients (0.15) in the ticagrelor group (HR, 3.99; 95% CI, 1.74-9.14; P = .001). Moreover, more patients in the ticagrelor/aspirin group experienced a composite of intracranial hemorrhage or fatal bleeding compared with the aspirin-only group (0.4% vs 0.1%). Fatal bleeding occurred in 0.2% of patients in the ticagrelor/aspirin group versus 0.1% of patients in the aspirin group. More patients in the ticagrelor-aspirin group permanently discontinued the treatment because of bleeding than in the aspirin-only group (2.8% vs. 0.6%).

“The benefit from treatment with ticagrelor/aspirin, as compared with aspirin alone, would be expected to result in a number needed to treat of 92 to prevent one primary outcome event, and a number needed to harm of 263 for severe bleeding,” the authors noted.
 

Risks versus benefits

Commenting on the study, Konark Malhotra, MD, a vascular neurologist at Allegheny Health Network, Pittsburgh, noted that ticagrelor is an antiplatelet medication “that adds to the armamentarium of stroke neurologists for the treatment of mild acute ischemic or high-risk TIA patients.” Dr. Malhotra, who was not involved with the study, added that the “combined use of ticagrelor and aspirin is effective in the reduction of ischemic events, however, at the expense of increased risk of bleeding events.”

In an accompanying editorial, Peter Rothwell, MD, PhD, of the Wolfson Center for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences at the University of Oxford (England) who was not involved with the study, suggested that the “bleeding risk associated with ticagrelor and aspirin might exceed the benefit among lower-risk patients who make up the majority in practice, and so the results should not be overgeneralized.” Moreover, “regardless of which combination of antiplatelet therapy is favored for the high-risk minority, all patients should receive aspirin immediately after TIA, unless aspirin is contraindicated.”

He noted that “too many patients are sent home from emergency departments without this simple treatment that substantially reduces the risk and severity of early recurrent stroke.”

The study was supported by AstraZeneca. Dr. Johnston has received a grant from AstraZeneca and nonfinancial support from SANOFI. Dr. Rothwell has received personal fees from Bayer and BMS. Dr. Malhotra has disclosed no relevant financial relationships.

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

The combination of ticagrelor and aspirin is superior to aspirin alone in reducing the risk for secondary stroke, transient ischemic attack (TIA), and death, new data show. However, severe bleeding was more common in the ticagrelor/aspirin group than in the aspirin-only group.

“We found that ticagrelor plus aspirin reduced the risk of stroke or death, compared to aspirin alone in patients presenting acutely with stroke or TIA,” reported lead author S. Claiborne Johnston, MD, PhD, dean and vice president for medical affairs, Dell Medical School, the University of Texas, Austin.

Although the combination also increased the risk for major hemorrhage, that increase was small and would not overwhelm the benefit, he said.

The study was published online July 16 in The New England Journal of Medicine.
 

Attractive properties

“Lots of patients have stroke in the days to weeks after first presenting with a stroke or TIA,” said Dr. Johnston, who is also the Frank and Charmaine Denius Distinguished Dean’s Chair at Dell Medical School. “Aspirin has been the standard of care but is only partially effective. Clopidogrel plus aspirin is another option that has recently been proven, [but] ticagrelor has attractive properties as an antiplatelet agent and works synergistically with aspirin,” he added.

Ticagrelor is a direct-acting antiplatelet agent that does not depend on metabolic activation and that “reversibly binds” and inhibits the P2Y12 receptor on platelets. Previous research has evaluated clopidogrel and aspirin for the secondary prevention of ischemic stroke or TIA. In an earlier trial, ticagrelor was no better than aspirin in preventing these subsequent events. However, the investigators noted that the combination of the two drugs has not been well studied.

The randomized, placebo-controlled, double-blind trial involved 11,016 patients at 414 sites in 28 countries. Patients who had experienced mild to moderate acute noncardioembolic ischemic stroke (mean age, 65 years; 39% women; roughly 54% White) were randomly assigned to receive either ticagrelor plus aspirin (n = 5,523) or aspirin alone (n = 5,493) for 30 days. Of these patients, 91% had sustained a stroke, and 9% had sustained a TIA.

Thirty days was chosen as the treatment period because the risk for subsequent stroke tends to occur mainly in the first month after an acute ischemic stroke or TIA. The primary outcome was “a composite of stroke or death in a time-to-first-event analysis from randomization to 30 days of follow-up.” For the study, “stroke” encompassed ischemic, hemorrhagic, or stroke of undetermined type, and “death” included deaths of all causes. Secondary outcomes included first subsequent ischemic stroke and disability (defined as a score of >1 on the Rankin Scale).

Almost all patients (99.5%) were taking aspirin during the treatment period, and most were also taking an antihypertensive and a statin (74% and 83%, respectively).

Patients in the ticagrelor/aspirin group had fewer primary-outcome events in comparison with those in the aspirin-only group (303 patients [5.5%] vs. 362 patients [6.6%]; hazard ratio, 0.83; 95% confidence interval, 0.71-0.96; P = 0.02). Incidence of subsequent ischemic stroke were similarly lower in the ticagrelor/aspirin group in comparison with the aspirin-only group (276 patients [5.0%] vs. 345 patients [6.3%]; HR, 0.79; 95% CI, 0.68-0.93; P = .004).

On the other hand, there was no significant difference between the groups in the incidence of overall disability (23.8% of the patients in the ticagrelor/aspirin group and in 24.1% of the patients in the aspirin group; odds ratio, 0.98; 95% CI, 0.89-1.07; P = .61).

There were differences between the groups in severe bleeding, which occurred in 28 patients (0.5%) in the ticagrelor/aspirin group and in seven patients (0.15) in the ticagrelor group (HR, 3.99; 95% CI, 1.74-9.14; P = .001). Moreover, more patients in the ticagrelor/aspirin group experienced a composite of intracranial hemorrhage or fatal bleeding compared with the aspirin-only group (0.4% vs 0.1%). Fatal bleeding occurred in 0.2% of patients in the ticagrelor/aspirin group versus 0.1% of patients in the aspirin group. More patients in the ticagrelor-aspirin group permanently discontinued the treatment because of bleeding than in the aspirin-only group (2.8% vs. 0.6%).

“The benefit from treatment with ticagrelor/aspirin, as compared with aspirin alone, would be expected to result in a number needed to treat of 92 to prevent one primary outcome event, and a number needed to harm of 263 for severe bleeding,” the authors noted.
 

Risks versus benefits

Commenting on the study, Konark Malhotra, MD, a vascular neurologist at Allegheny Health Network, Pittsburgh, noted that ticagrelor is an antiplatelet medication “that adds to the armamentarium of stroke neurologists for the treatment of mild acute ischemic or high-risk TIA patients.” Dr. Malhotra, who was not involved with the study, added that the “combined use of ticagrelor and aspirin is effective in the reduction of ischemic events, however, at the expense of increased risk of bleeding events.”

In an accompanying editorial, Peter Rothwell, MD, PhD, of the Wolfson Center for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences at the University of Oxford (England) who was not involved with the study, suggested that the “bleeding risk associated with ticagrelor and aspirin might exceed the benefit among lower-risk patients who make up the majority in practice, and so the results should not be overgeneralized.” Moreover, “regardless of which combination of antiplatelet therapy is favored for the high-risk minority, all patients should receive aspirin immediately after TIA, unless aspirin is contraindicated.”

He noted that “too many patients are sent home from emergency departments without this simple treatment that substantially reduces the risk and severity of early recurrent stroke.”

The study was supported by AstraZeneca. Dr. Johnston has received a grant from AstraZeneca and nonfinancial support from SANOFI. Dr. Rothwell has received personal fees from Bayer and BMS. Dr. Malhotra has disclosed no relevant financial relationships.

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

THE CASE

A 50-year-old man presented to the primary care office for evaluation of foot pain. The day before, his left fifth toe had become exquisitely tender. He distinctly remembered that when he awoke, there was no discoloration or pain, but the toe later became “purple.” He denied any trauma. His medical record was notable for an extensive smoking history and a family history of early cardiovascular disease.

The patient appeared well but in obvious distress, secondary to the pain. His vital signs were unremarkable. His head, neck, lung, and cardiac exams revealed no abnormalities. Physical examination revealed a left fifth toe that was dusky purple and warm to the touch. Pain disproportionate to examination was noted on the anterior aspect of the toe, with limited range of motion. The patient walked with a compensated gait. Pulses were palpable on the posterior tibial (PT) and dorsalis pedis (DP) regions.

DIAGNOSIS

Based on our exam findings, we suspected a vascular injury and recommended an emergency consult by Podiatry, for which he was scheduled the following morning. The podiatric evaluation confirmed concern for a vascular injury and prompted a request for an emergent evaluation by Vascular Surgery.

The patient was seen emergently on Day 4 for a vascular surgery evaluation. Examination at that time showed a nearly absent femoral pulse on the left side and diminished and monophasic DP and PT pulses. His left foot demonstrated nonblanchable purpura that was clinically consistent with cholesterol embolization syndrome (CES).

We calculated the patient’s ankle-brachial index, and computed tomography angiography (CTA) was performed. While results were pending, the patient was started on aspirin 81 mg, clopidogrel 75 mg, and atorvastatin 40 mg, for a suspected slowly progressing iliac artery stenosis with a resulting acute atheroembolic event.

The CTA report showed a high-grade stenosis at the bifurcation of the left iliac artery, extending into both external and internal arteries. Of note, mild atherosclerotic disease without significant occlusion and runoff to the foot was observed into the tibial arteries. The stenosis extended into the profonda femoris artery, as well.

DISCUSSION

Atherosclerotic plaques are commonly encountered in patients with atherosclerotic disease; however, there are 2 varieties of emboli that arise from these plaques and one is often overlooked.^1-4 The more common of these variants, thromboemboli, originates from an atherosclerotic plaque and can become lodged in a medium or large vessel as a single embolus.

Continue to: By contrast...

By contrast, atheroemboli (commonly known as cholesterol emboli or cholesterol crystal embolization) originate from atherosclerotic plaques in the aorta or another large artery,⁵ which are prone to embolize if the underlying plaque experiences stress. As the plaque erodes, cholesterol crystals break off and embolize distally. These smaller crystals flood into the circulation, allowing a shower of emboli over time to occlude the arterioles. As occlusion spreads through the arterioles, multiple organ systems are affected. (It was previously thought that procedure-associated cases were common, but a literature review has not borne this out.⁵)

The shower of emboli often triggers a systemic inflammatory response, causing nondescript abnormalities of laboratory inflammatory markers.^6,7 Interestingly, hypereosinophilia is noted in about 80% of patients with CES.⁸It is not uncommon for atheroemboli of the lower extremity to manifest, as it did in this case, as “blue toe syndrome.”

No disease-specific testing. A confounding factor in validating the diagnosis of CES is the lack of disease-specific testing. However, CES should be considered in a patient with acute kidney injury and hypereosinophilia. Making the diagnosis requires a high degree of clinical suspicion. Any organ can be affected, although the brain, kidneys, gastrointestinal tract, skin, and skeletal muscles of the lower extremities are most frequently involved.⁹ If left undiagnosed, the results can be devastating: slow and chronic injury to a variety of organ systems over time, which may not be recognized as a harbinger of an insidious underlying process causing end-organ damage.

Technically, definitive diagnosis can be made by biopsy of an affected organ. However, biopsy’s utility is limited due to potential for sampling error, accessibility (as noted, the location of the involved organ[s] may make biopsy nearly impossible without additional surgical risk⁹), and risk of poor healing to the biopsy site.¹⁰

Treatment is two-fold: supportive care for the affected end organ and prevention of subsequent embolic events. The latter entails aggressive risk factor reduction strategies, such as smoking cessation, statin therapy, blood pressure control, and blood sugar control. Warfarin is not recommended for treatment of CES due to the risk of further plaque rupture, hemorrhage, acute and chronic renal failure, and cholesterol microembolization to other organs.^11,12

Continue to: Our patient

Our patient. After testing confirmed the diagnosis, the patient underwent an angioplasty. A stent was placed in his left iliac artery. He was continued on antiplatelet and statin therapy and was again counseled regarding smoking cessation.

THE TAKEAWAY

When patients present with symptoms suggestive of a vascular origin, consider CES. Although it can affect a multitude of organs, acute kidney injury and hypereosinophilia are the most common signs. Immediate intervention is required to save the affected organ; strategizing to reduce the risk for further embolic events is also key.

Warfarin is not recommended for treatment of cholesterol embolization syndrome due to the risk of further plaque rupture, hemorrhage, and cholesterol microembolization to other organs.

Prompt recognition of vascular emergencies, including those that are harbingers of atherosclerotic disease, is essential. As clinicians, it is imperative that we use all resources to address significant population health burdens. If CES is more prevalent than commonly thought, consideration should be given to increasing education about early detection and treatment of this disorder, including the reinforcement of primary prevention and aggressive treatment of risk factors for atherosclerotic cardiovascular disease.

CORRESPONDENCE
Meagan Vermeulen, MD, FAAFP, Department of Family Medicine, Rowan University School of Osteopathic Medicine, 42 East Laurel Road, Suite 2100A, Stratford, NJ 08084; vermeulen@rowan.edu

THE CASE

A 50-year-old man presented to the primary care office for evaluation of foot pain. The day before, his left fifth toe had become exquisitely tender. He distinctly remembered that when he awoke, there was no discoloration or pain, but the toe later became “purple.” He denied any trauma. His medical record was notable for an extensive smoking history and a family history of early cardiovascular disease.

The patient appeared well but in obvious distress, secondary to the pain. His vital signs were unremarkable. His head, neck, lung, and cardiac exams revealed no abnormalities. Physical examination revealed a left fifth toe that was dusky purple and warm to the touch. Pain disproportionate to examination was noted on the anterior aspect of the toe, with limited range of motion. The patient walked with a compensated gait. Pulses were palpable on the posterior tibial (PT) and dorsalis pedis (DP) regions.

DIAGNOSIS

Based on our exam findings, we suspected a vascular injury and recommended an emergency consult by Podiatry, for which he was scheduled the following morning. The podiatric evaluation confirmed concern for a vascular injury and prompted a request for an emergent evaluation by Vascular Surgery.

The patient was seen emergently on Day 4 for a vascular surgery evaluation. Examination at that time showed a nearly absent femoral pulse on the left side and diminished and monophasic DP and PT pulses. His left foot demonstrated nonblanchable purpura that was clinically consistent with cholesterol embolization syndrome (CES).

We calculated the patient’s ankle-brachial index, and computed tomography angiography (CTA) was performed. While results were pending, the patient was started on aspirin 81 mg, clopidogrel 75 mg, and atorvastatin 40 mg, for a suspected slowly progressing iliac artery stenosis with a resulting acute atheroembolic event.

The CTA report showed a high-grade stenosis at the bifurcation of the left iliac artery, extending into both external and internal arteries. Of note, mild atherosclerotic disease without significant occlusion and runoff to the foot was observed into the tibial arteries. The stenosis extended into the profonda femoris artery, as well.

DISCUSSION

Atherosclerotic plaques are commonly encountered in patients with atherosclerotic disease; however, there are 2 varieties of emboli that arise from these plaques and one is often overlooked.^1-4 The more common of these variants, thromboemboli, originates from an atherosclerotic plaque and can become lodged in a medium or large vessel as a single embolus.

Continue to: By contrast...

By contrast, atheroemboli (commonly known as cholesterol emboli or cholesterol crystal embolization) originate from atherosclerotic plaques in the aorta or another large artery,⁵ which are prone to embolize if the underlying plaque experiences stress. As the plaque erodes, cholesterol crystals break off and embolize distally. These smaller crystals flood into the circulation, allowing a shower of emboli over time to occlude the arterioles. As occlusion spreads through the arterioles, multiple organ systems are affected. (It was previously thought that procedure-associated cases were common, but a literature review has not borne this out.⁵)

The shower of emboli often triggers a systemic inflammatory response, causing nondescript abnormalities of laboratory inflammatory markers.^6,7 Interestingly, hypereosinophilia is noted in about 80% of patients with CES.⁸It is not uncommon for atheroemboli of the lower extremity to manifest, as it did in this case, as “blue toe syndrome.”

No disease-specific testing. A confounding factor in validating the diagnosis of CES is the lack of disease-specific testing. However, CES should be considered in a patient with acute kidney injury and hypereosinophilia. Making the diagnosis requires a high degree of clinical suspicion. Any organ can be affected, although the brain, kidneys, gastrointestinal tract, skin, and skeletal muscles of the lower extremities are most frequently involved.⁹ If left undiagnosed, the results can be devastating: slow and chronic injury to a variety of organ systems over time, which may not be recognized as a harbinger of an insidious underlying process causing end-organ damage.

Technically, definitive diagnosis can be made by biopsy of an affected organ. However, biopsy’s utility is limited due to potential for sampling error, accessibility (as noted, the location of the involved organ[s] may make biopsy nearly impossible without additional surgical risk⁹), and risk of poor healing to the biopsy site.¹⁰

Treatment is two-fold: supportive care for the affected end organ and prevention of subsequent embolic events. The latter entails aggressive risk factor reduction strategies, such as smoking cessation, statin therapy, blood pressure control, and blood sugar control. Warfarin is not recommended for treatment of CES due to the risk of further plaque rupture, hemorrhage, acute and chronic renal failure, and cholesterol microembolization to other organs.^11,12

Continue to: Our patient

Our patient. After testing confirmed the diagnosis, the patient underwent an angioplasty. A stent was placed in his left iliac artery. He was continued on antiplatelet and statin therapy and was again counseled regarding smoking cessation.

THE TAKEAWAY

When patients present with symptoms suggestive of a vascular origin, consider CES. Although it can affect a multitude of organs, acute kidney injury and hypereosinophilia are the most common signs. Immediate intervention is required to save the affected organ; strategizing to reduce the risk for further embolic events is also key.

Warfarin is not recommended for treatment of cholesterol embolization syndrome due to the risk of further plaque rupture, hemorrhage, and cholesterol microembolization to other organs.

Prompt recognition of vascular emergencies, including those that are harbingers of atherosclerotic disease, is essential. As clinicians, it is imperative that we use all resources to address significant population health burdens. If CES is more prevalent than commonly thought, consideration should be given to increasing education about early detection and treatment of this disorder, including the reinforcement of primary prevention and aggressive treatment of risk factors for atherosclerotic cardiovascular disease.

CORRESPONDENCE
Meagan Vermeulen, MD, FAAFP, Department of Family Medicine, Rowan University School of Osteopathic Medicine, 42 East Laurel Road, Suite 2100A, Stratford, NJ 08084; vermeulen@rowan.edu

THE CASE

A 50-year-old man presented to the primary care office for evaluation of foot pain. The day before, his left fifth toe had become exquisitely tender. He distinctly remembered that when he awoke, there was no discoloration or pain, but the toe later became “purple.” He denied any trauma. His medical record was notable for an extensive smoking history and a family history of early cardiovascular disease.

The patient appeared well but in obvious distress, secondary to the pain. His vital signs were unremarkable. His head, neck, lung, and cardiac exams revealed no abnormalities. Physical examination revealed a left fifth toe that was dusky purple and warm to the touch. Pain disproportionate to examination was noted on the anterior aspect of the toe, with limited range of motion. The patient walked with a compensated gait. Pulses were palpable on the posterior tibial (PT) and dorsalis pedis (DP) regions.

DIAGNOSIS

Based on our exam findings, we suspected a vascular injury and recommended an emergency consult by Podiatry, for which he was scheduled the following morning. The podiatric evaluation confirmed concern for a vascular injury and prompted a request for an emergent evaluation by Vascular Surgery.

The patient was seen emergently on Day 4 for a vascular surgery evaluation. Examination at that time showed a nearly absent femoral pulse on the left side and diminished and monophasic DP and PT pulses. His left foot demonstrated nonblanchable purpura that was clinically consistent with cholesterol embolization syndrome (CES).

We calculated the patient’s ankle-brachial index, and computed tomography angiography (CTA) was performed. While results were pending, the patient was started on aspirin 81 mg, clopidogrel 75 mg, and atorvastatin 40 mg, for a suspected slowly progressing iliac artery stenosis with a resulting acute atheroembolic event.

The CTA report showed a high-grade stenosis at the bifurcation of the left iliac artery, extending into both external and internal arteries. Of note, mild atherosclerotic disease without significant occlusion and runoff to the foot was observed into the tibial arteries. The stenosis extended into the profonda femoris artery, as well.

DISCUSSION

Atherosclerotic plaques are commonly encountered in patients with atherosclerotic disease; however, there are 2 varieties of emboli that arise from these plaques and one is often overlooked.^1-4 The more common of these variants, thromboemboli, originates from an atherosclerotic plaque and can become lodged in a medium or large vessel as a single embolus.

Continue to: By contrast...

By contrast, atheroemboli (commonly known as cholesterol emboli or cholesterol crystal embolization) originate from atherosclerotic plaques in the aorta or another large artery,⁵ which are prone to embolize if the underlying plaque experiences stress. As the plaque erodes, cholesterol crystals break off and embolize distally. These smaller crystals flood into the circulation, allowing a shower of emboli over time to occlude the arterioles. As occlusion spreads through the arterioles, multiple organ systems are affected. (It was previously thought that procedure-associated cases were common, but a literature review has not borne this out.⁵)

The shower of emboli often triggers a systemic inflammatory response, causing nondescript abnormalities of laboratory inflammatory markers.^6,7 Interestingly, hypereosinophilia is noted in about 80% of patients with CES.⁸It is not uncommon for atheroemboli of the lower extremity to manifest, as it did in this case, as “blue toe syndrome.”

No disease-specific testing. A confounding factor in validating the diagnosis of CES is the lack of disease-specific testing. However, CES should be considered in a patient with acute kidney injury and hypereosinophilia. Making the diagnosis requires a high degree of clinical suspicion. Any organ can be affected, although the brain, kidneys, gastrointestinal tract, skin, and skeletal muscles of the lower extremities are most frequently involved.⁹ If left undiagnosed, the results can be devastating: slow and chronic injury to a variety of organ systems over time, which may not be recognized as a harbinger of an insidious underlying process causing end-organ damage.

Technically, definitive diagnosis can be made by biopsy of an affected organ. However, biopsy’s utility is limited due to potential for sampling error, accessibility (as noted, the location of the involved organ[s] may make biopsy nearly impossible without additional surgical risk⁹), and risk of poor healing to the biopsy site.¹⁰

Treatment is two-fold: supportive care for the affected end organ and prevention of subsequent embolic events. The latter entails aggressive risk factor reduction strategies, such as smoking cessation, statin therapy, blood pressure control, and blood sugar control. Warfarin is not recommended for treatment of CES due to the risk of further plaque rupture, hemorrhage, acute and chronic renal failure, and cholesterol microembolization to other organs.^11,12

Continue to: Our patient

Our patient. After testing confirmed the diagnosis, the patient underwent an angioplasty. A stent was placed in his left iliac artery. He was continued on antiplatelet and statin therapy and was again counseled regarding smoking cessation.

THE TAKEAWAY

When patients present with symptoms suggestive of a vascular origin, consider CES. Although it can affect a multitude of organs, acute kidney injury and hypereosinophilia are the most common signs. Immediate intervention is required to save the affected organ; strategizing to reduce the risk for further embolic events is also key.

Warfarin is not recommended for treatment of cholesterol embolization syndrome due to the risk of further plaque rupture, hemorrhage, and cholesterol microembolization to other organs.

Prompt recognition of vascular emergencies, including those that are harbingers of atherosclerotic disease, is essential. As clinicians, it is imperative that we use all resources to address significant population health burdens. If CES is more prevalent than commonly thought, consideration should be given to increasing education about early detection and treatment of this disorder, including the reinforcement of primary prevention and aggressive treatment of risk factors for atherosclerotic cardiovascular disease.

CORRESPONDENCE
Meagan Vermeulen, MD, FAAFP, Department of Family Medicine, Rowan University School of Osteopathic Medicine, 42 East Laurel Road, Suite 2100A, Stratford, NJ 08084; vermeulen@rowan.edu

Young adult smokers who stop smoking in the first year after an initial myocardial infarction are far less likely to die over the next 10 years than their peers who continue to smoke. Yet nearly two-thirds keep smoking after the event, according to new data from the Partners YOUNG-MI Registry.

“Smoking is one of the most common risk factors for developing an MI at a young age. ... This reinforces the need to have more young individuals avoid, or quit, the use of tobacco,” Ron Blankstein, MD, Brigham and Women’s Hospital and Harvard Medical School, Boston, said in an interview.

Yet, the finding that 62% of young adults continue to smoke 1 year after MI points to an “enormous need for better smoking cessation efforts following a heart attack,” he said.
 

“Powerful” message for clinicians

“This study joins an incredibly powerful body of evidence that says if you quit smoking, you’re going to live longer,” said Michael Fiore, MD, MPH, MBA, director of the University of Wisconsin Center for Tobacco Research and Intervention, Madison, who wasn’t involved in the study.

“As physicians, there is nothing we can do that will have a greater impact for our patients than quitting smoking. The study is a powerful call for clinicians to intervene with their patients that smoke – both if you have an MI or if you don’t,” Dr. Fiore told this news organization.

The study involved 2,072 individuals 50 years or younger (median age, 45 years; 81% male) who were hospitalized for an initial MI at two large academic medical centers in Boston. Of these, 33.9% were never-smokers, 13.6% were former smokers, and 52.5% were smokers at the time of their MI.

During a median follow-up of 10.2 years, those who quit smoking had a significantly lower rate of death from any cause (unadjusted hazard ratio, 0.35; 95% confidence interval, 0.19-0.63; P < .001) and a cardiovascular cause (HR, 0.29; 95% CI, 0.11-0.79; P = .02), relative to those who continued to smoke.

The results remained statistically significant in a propensity-matched analysis for both all-cause (HR, 0.30; 95% CI, 0.16-0.56; P < .001) and CV mortality (HR, 0.19; 95% CI, 0.06-0.56; P = .003).

“Although patients who quit smoking were similar to those who continued to smoke with respect to their baseline characteristics, smoking cessation was associated with an approximate 70%-80% reduction in all-cause and CV mortality,” the authors note in their article, published online July 8 in JAMA Network Open.

They say it’s also noteworthy that long-term death rates of never-smokers and former smokers who quit before the MI were nearly identical.

‘A failure of our health care system’

The bottom line, said Dr. Blankstein, is that it is “never too late to quit, and those who experience an MI should do so right away. Our health care system must help promote such efforts, as there is immense room for improvement.”

Dr. Fiore said: “When I see an article like this, it just reminds me that, if you’re really thinking about staying healthy, there is nothing better you can do to improve the quality and longevity of your life than quitting smoking.”

The observation that many patients continue to smoke after MI is a “failure of our health care system, and it’s an individual failure in that these individuals are not able to overcome their powerful nicotine dependence. It’s an unfortunate occurrence that’s resulting in unnecessary deaths,” said Dr. Fiore.

There is no “magic bullet” to overcome nicotine addiction, but there are approved treatments that can “substantially boost quit rates,” he noted.

The two most effective smoking-cessation treatments are varenicline (Chantix) and combination nicotine replacement therapy, a patch combined ideally with nicotine mini lozenges, particularly when combined with some brief counseling, said Fiore.

He encourages cardiologists to get their patients to commit to quitting and then link them to resources such as 1-800-QUIT-NOW or SmokeFree.gov.

Funding for the study was provided by grants from the National Heart, Lung, and Blood Institute. Dr. Blankstein reported receiving research support from Amgen and Astellas. Dr. Fiore had no relevant disclosures.

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

Young adult smokers who stop smoking in the first year after an initial myocardial infarction are far less likely to die over the next 10 years than their peers who continue to smoke. Yet nearly two-thirds keep smoking after the event, according to new data from the Partners YOUNG-MI Registry.

“Smoking is one of the most common risk factors for developing an MI at a young age. ... This reinforces the need to have more young individuals avoid, or quit, the use of tobacco,” Ron Blankstein, MD, Brigham and Women’s Hospital and Harvard Medical School, Boston, said in an interview.

Yet, the finding that 62% of young adults continue to smoke 1 year after MI points to an “enormous need for better smoking cessation efforts following a heart attack,” he said.
 

“Powerful” message for clinicians

“This study joins an incredibly powerful body of evidence that says if you quit smoking, you’re going to live longer,” said Michael Fiore, MD, MPH, MBA, director of the University of Wisconsin Center for Tobacco Research and Intervention, Madison, who wasn’t involved in the study.

“As physicians, there is nothing we can do that will have a greater impact for our patients than quitting smoking. The study is a powerful call for clinicians to intervene with their patients that smoke – both if you have an MI or if you don’t,” Dr. Fiore told this news organization.

The study involved 2,072 individuals 50 years or younger (median age, 45 years; 81% male) who were hospitalized for an initial MI at two large academic medical centers in Boston. Of these, 33.9% were never-smokers, 13.6% were former smokers, and 52.5% were smokers at the time of their MI.

During a median follow-up of 10.2 years, those who quit smoking had a significantly lower rate of death from any cause (unadjusted hazard ratio, 0.35; 95% confidence interval, 0.19-0.63; P < .001) and a cardiovascular cause (HR, 0.29; 95% CI, 0.11-0.79; P = .02), relative to those who continued to smoke.

The results remained statistically significant in a propensity-matched analysis for both all-cause (HR, 0.30; 95% CI, 0.16-0.56; P < .001) and CV mortality (HR, 0.19; 95% CI, 0.06-0.56; P = .003).

“Although patients who quit smoking were similar to those who continued to smoke with respect to their baseline characteristics, smoking cessation was associated with an approximate 70%-80% reduction in all-cause and CV mortality,” the authors note in their article, published online July 8 in JAMA Network Open.

They say it’s also noteworthy that long-term death rates of never-smokers and former smokers who quit before the MI were nearly identical.

‘A failure of our health care system’

The bottom line, said Dr. Blankstein, is that it is “never too late to quit, and those who experience an MI should do so right away. Our health care system must help promote such efforts, as there is immense room for improvement.”

Dr. Fiore said: “When I see an article like this, it just reminds me that, if you’re really thinking about staying healthy, there is nothing better you can do to improve the quality and longevity of your life than quitting smoking.”

The observation that many patients continue to smoke after MI is a “failure of our health care system, and it’s an individual failure in that these individuals are not able to overcome their powerful nicotine dependence. It’s an unfortunate occurrence that’s resulting in unnecessary deaths,” said Dr. Fiore.

There is no “magic bullet” to overcome nicotine addiction, but there are approved treatments that can “substantially boost quit rates,” he noted.

The two most effective smoking-cessation treatments are varenicline (Chantix) and combination nicotine replacement therapy, a patch combined ideally with nicotine mini lozenges, particularly when combined with some brief counseling, said Fiore.

He encourages cardiologists to get their patients to commit to quitting and then link them to resources such as 1-800-QUIT-NOW or SmokeFree.gov.

Funding for the study was provided by grants from the National Heart, Lung, and Blood Institute. Dr. Blankstein reported receiving research support from Amgen and Astellas. Dr. Fiore had no relevant disclosures.

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

Young adult smokers who stop smoking in the first year after an initial myocardial infarction are far less likely to die over the next 10 years than their peers who continue to smoke. Yet nearly two-thirds keep smoking after the event, according to new data from the Partners YOUNG-MI Registry.

“Smoking is one of the most common risk factors for developing an MI at a young age. ... This reinforces the need to have more young individuals avoid, or quit, the use of tobacco,” Ron Blankstein, MD, Brigham and Women’s Hospital and Harvard Medical School, Boston, said in an interview.

Yet, the finding that 62% of young adults continue to smoke 1 year after MI points to an “enormous need for better smoking cessation efforts following a heart attack,” he said.
 

“Powerful” message for clinicians

“This study joins an incredibly powerful body of evidence that says if you quit smoking, you’re going to live longer,” said Michael Fiore, MD, MPH, MBA, director of the University of Wisconsin Center for Tobacco Research and Intervention, Madison, who wasn’t involved in the study.

“As physicians, there is nothing we can do that will have a greater impact for our patients than quitting smoking. The study is a powerful call for clinicians to intervene with their patients that smoke – both if you have an MI or if you don’t,” Dr. Fiore told this news organization.

The study involved 2,072 individuals 50 years or younger (median age, 45 years; 81% male) who were hospitalized for an initial MI at two large academic medical centers in Boston. Of these, 33.9% were never-smokers, 13.6% were former smokers, and 52.5% were smokers at the time of their MI.

During a median follow-up of 10.2 years, those who quit smoking had a significantly lower rate of death from any cause (unadjusted hazard ratio, 0.35; 95% confidence interval, 0.19-0.63; P < .001) and a cardiovascular cause (HR, 0.29; 95% CI, 0.11-0.79; P = .02), relative to those who continued to smoke.

The results remained statistically significant in a propensity-matched analysis for both all-cause (HR, 0.30; 95% CI, 0.16-0.56; P < .001) and CV mortality (HR, 0.19; 95% CI, 0.06-0.56; P = .003).

“Although patients who quit smoking were similar to those who continued to smoke with respect to their baseline characteristics, smoking cessation was associated with an approximate 70%-80% reduction in all-cause and CV mortality,” the authors note in their article, published online July 8 in JAMA Network Open.

They say it’s also noteworthy that long-term death rates of never-smokers and former smokers who quit before the MI were nearly identical.

‘A failure of our health care system’

The bottom line, said Dr. Blankstein, is that it is “never too late to quit, and those who experience an MI should do so right away. Our health care system must help promote such efforts, as there is immense room for improvement.”

Dr. Fiore said: “When I see an article like this, it just reminds me that, if you’re really thinking about staying healthy, there is nothing better you can do to improve the quality and longevity of your life than quitting smoking.”

The observation that many patients continue to smoke after MI is a “failure of our health care system, and it’s an individual failure in that these individuals are not able to overcome their powerful nicotine dependence. It’s an unfortunate occurrence that’s resulting in unnecessary deaths,” said Dr. Fiore.

There is no “magic bullet” to overcome nicotine addiction, but there are approved treatments that can “substantially boost quit rates,” he noted.

The two most effective smoking-cessation treatments are varenicline (Chantix) and combination nicotine replacement therapy, a patch combined ideally with nicotine mini lozenges, particularly when combined with some brief counseling, said Fiore.

He encourages cardiologists to get their patients to commit to quitting and then link them to resources such as 1-800-QUIT-NOW or SmokeFree.gov.

Funding for the study was provided by grants from the National Heart, Lung, and Blood Institute. Dr. Blankstein reported receiving research support from Amgen and Astellas. Dr. Fiore had no relevant disclosures.

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

The first order of business in the long-awaited, recently released Centers for Medicare & Medicaid Services (CMS) proposed national coverage decision (NCD) for transcatheter mitral valve repair (TMVR) was to get rid of its familiar moniker.

The document tosses the term TMVR in favor of transcatheter edge-to-edge repair (TEER) “to more precisely define the treatment addressed in this NCD” and differentiate it from other therapies that repair or replace the mitral valve.

(In an off-the-cuff Twitter poll launched right after the CMS document’s release, 80.3% of respondents answered that they “hate” the new acronym and the remainder said they “love” it; those two were the poll’s only choices.)

The NCD proposal goes on to say that CMS coverage of TEER would expand to include treatment of symptomatic moderate-to-severe or severe functional mitral regurgitation (MR) when used with maximally tolerated guideline-directed medical therapy.

The proposed NCD has been expected since March 2019 when the US Food and Drug Administration (FDA) approved the MitraClip (Abbott Vascular) for secondary functional MR. Medicare has covered MitraClip for primary degenerative MR since 2014.

Abbott announced in October 2019 that it would ramp up production of the MitraClip, which is currently the only FDA-approved TEER device.

Further specifications

Even as the new proposed NCD would add CMS coverage for functional MR, it would also decline a coverage statement for degenerative MR. Instead, it proposes to leave such coverage decisions to local Medical Administrative Contractors (MACs), given a relatively low incidence of clip intervention for degenerative MR. Less than 1% of the Medicare population undergo TEER of the mitral valve for that indication, the document says.

“The MACs are structured to be able to take into account local patient, physician, and institutional factors, which are especially important when overall prevalence is very low.”

The proposal also emphasizes that patients undergoing such covered TEER procedures be “under the care of a heart failure physician specialist experienced in the care and treatment of mitral valve disease,» with additional care provided by a heart team that includes a cardiac surgeon, interventional cardiologist, interventional echocardiographer.

The new document is generally consistent with a Consensus Statement from the American Association for Thoracic Surgery, the American College of Cardiology (ACC), the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons published in December 2019 and covered then by theheart.org / Medscape Cardiology.

In anticipation the CMS coverage proposal, the ACC earlier this year published a Focused Update of the 2017 Expert Consensus Decision Pathway on the Management of Mitral Regurgitation to reflect new evidence in the field, mainly the recent clinical trial data on functional MR from the MITRA-FR and COAPT trials.

“The proposed criteria are nicely guided by the multisociety consensus document, which sought to foster optimal patient outcomes while also maintaining access to TEER,” Sammy Elmariah, MD, MPH, from Massachusetts General Hospital in Boston, commented by email.

“These criteria, in conjunction with results of the COAPT trial, establish TEER as the standard of care for patients with symptomatic functional MR despite guideline-directed medical therapy who do not possess an alternative indication for cardiac surgery,” said Elmariah, a coauthor on both the Consensus Statement and the Focused Update.

The proposed NCD seems “reasonable,” cardiothoracic surgeon Michael J. Reardon, MD, Houston Methodist Hospital, said by email. But he thought there might be some objections to the requirement for TEER centers to have a surgery program with a minimum annual volume for mitral-valve surgeries.

The proposed NCD says a hospital must have “a surgical program that performs ≥25 total mitral valve surgical procedures for severe MR per year, of which at least 10 must be mitral valve repairs.”

“There is a very definite relationship between mitral valve surgery volume and surgical outcomes and between TEER volume and TEER outcomes, but no real relationship between mitral valve surgery volumes and TEER outcomes,” Reardon said. “A mitral valve surgery program is important, but how many cases do you need to be able to start and run a TEER program?”

Edwards Lifesciences is currently testing its own device for TEER: the PASCAL transcatheter mitral valve repair system. Early findings from the company’s ongoing CLASP IID trial, a head-to-head comparison of Pascal and MitraClip, are expected in December 2023.

CMS is seeking comments on the proposed national coverage determination, and will render a final decision within 60 days of the end of the 30-day public comment period.

Elmariah discloses receiving research grants from the American Heart Association, the National Institutes of Health, Edwards Lifesciences, Svelte Medical, and Medtronic, and consulting fees from AstraZeneca. Reardon recently reported no relevant conflicts of interest.

This article first appeared on Medscape.com.

The first order of business in the long-awaited, recently released Centers for Medicare & Medicaid Services (CMS) proposed national coverage decision (NCD) for transcatheter mitral valve repair (TMVR) was to get rid of its familiar moniker.

The document tosses the term TMVR in favor of transcatheter edge-to-edge repair (TEER) “to more precisely define the treatment addressed in this NCD” and differentiate it from other therapies that repair or replace the mitral valve.

(In an off-the-cuff Twitter poll launched right after the CMS document’s release, 80.3% of respondents answered that they “hate” the new acronym and the remainder said they “love” it; those two were the poll’s only choices.)

The NCD proposal goes on to say that CMS coverage of TEER would expand to include treatment of symptomatic moderate-to-severe or severe functional mitral regurgitation (MR) when used with maximally tolerated guideline-directed medical therapy.

The proposed NCD has been expected since March 2019 when the US Food and Drug Administration (FDA) approved the MitraClip (Abbott Vascular) for secondary functional MR. Medicare has covered MitraClip for primary degenerative MR since 2014.

Abbott announced in October 2019 that it would ramp up production of the MitraClip, which is currently the only FDA-approved TEER device.

Further specifications

Even as the new proposed NCD would add CMS coverage for functional MR, it would also decline a coverage statement for degenerative MR. Instead, it proposes to leave such coverage decisions to local Medical Administrative Contractors (MACs), given a relatively low incidence of clip intervention for degenerative MR. Less than 1% of the Medicare population undergo TEER of the mitral valve for that indication, the document says.

“The MACs are structured to be able to take into account local patient, physician, and institutional factors, which are especially important when overall prevalence is very low.”

The proposal also emphasizes that patients undergoing such covered TEER procedures be “under the care of a heart failure physician specialist experienced in the care and treatment of mitral valve disease,» with additional care provided by a heart team that includes a cardiac surgeon, interventional cardiologist, interventional echocardiographer.

The new document is generally consistent with a Consensus Statement from the American Association for Thoracic Surgery, the American College of Cardiology (ACC), the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons published in December 2019 and covered then by theheart.org / Medscape Cardiology.

In anticipation the CMS coverage proposal, the ACC earlier this year published a Focused Update of the 2017 Expert Consensus Decision Pathway on the Management of Mitral Regurgitation to reflect new evidence in the field, mainly the recent clinical trial data on functional MR from the MITRA-FR and COAPT trials.

“The proposed criteria are nicely guided by the multisociety consensus document, which sought to foster optimal patient outcomes while also maintaining access to TEER,” Sammy Elmariah, MD, MPH, from Massachusetts General Hospital in Boston, commented by email.

“These criteria, in conjunction with results of the COAPT trial, establish TEER as the standard of care for patients with symptomatic functional MR despite guideline-directed medical therapy who do not possess an alternative indication for cardiac surgery,” said Elmariah, a coauthor on both the Consensus Statement and the Focused Update.

The proposed NCD seems “reasonable,” cardiothoracic surgeon Michael J. Reardon, MD, Houston Methodist Hospital, said by email. But he thought there might be some objections to the requirement for TEER centers to have a surgery program with a minimum annual volume for mitral-valve surgeries.

The proposed NCD says a hospital must have “a surgical program that performs ≥25 total mitral valve surgical procedures for severe MR per year, of which at least 10 must be mitral valve repairs.”

“There is a very definite relationship between mitral valve surgery volume and surgical outcomes and between TEER volume and TEER outcomes, but no real relationship between mitral valve surgery volumes and TEER outcomes,” Reardon said. “A mitral valve surgery program is important, but how many cases do you need to be able to start and run a TEER program?”

Edwards Lifesciences is currently testing its own device for TEER: the PASCAL transcatheter mitral valve repair system. Early findings from the company’s ongoing CLASP IID trial, a head-to-head comparison of Pascal and MitraClip, are expected in December 2023.

CMS is seeking comments on the proposed national coverage determination, and will render a final decision within 60 days of the end of the 30-day public comment period.

Elmariah discloses receiving research grants from the American Heart Association, the National Institutes of Health, Edwards Lifesciences, Svelte Medical, and Medtronic, and consulting fees from AstraZeneca. Reardon recently reported no relevant conflicts of interest.

This article first appeared on Medscape.com.

The first order of business in the long-awaited, recently released Centers for Medicare & Medicaid Services (CMS) proposed national coverage decision (NCD) for transcatheter mitral valve repair (TMVR) was to get rid of its familiar moniker.

The document tosses the term TMVR in favor of transcatheter edge-to-edge repair (TEER) “to more precisely define the treatment addressed in this NCD” and differentiate it from other therapies that repair or replace the mitral valve.

(In an off-the-cuff Twitter poll launched right after the CMS document’s release, 80.3% of respondents answered that they “hate” the new acronym and the remainder said they “love” it; those two were the poll’s only choices.)

The NCD proposal goes on to say that CMS coverage of TEER would expand to include treatment of symptomatic moderate-to-severe or severe functional mitral regurgitation (MR) when used with maximally tolerated guideline-directed medical therapy.

The proposed NCD has been expected since March 2019 when the US Food and Drug Administration (FDA) approved the MitraClip (Abbott Vascular) for secondary functional MR. Medicare has covered MitraClip for primary degenerative MR since 2014.

Abbott announced in October 2019 that it would ramp up production of the MitraClip, which is currently the only FDA-approved TEER device.

Further specifications

Even as the new proposed NCD would add CMS coverage for functional MR, it would also decline a coverage statement for degenerative MR. Instead, it proposes to leave such coverage decisions to local Medical Administrative Contractors (MACs), given a relatively low incidence of clip intervention for degenerative MR. Less than 1% of the Medicare population undergo TEER of the mitral valve for that indication, the document says.

“The MACs are structured to be able to take into account local patient, physician, and institutional factors, which are especially important when overall prevalence is very low.”

The proposal also emphasizes that patients undergoing such covered TEER procedures be “under the care of a heart failure physician specialist experienced in the care and treatment of mitral valve disease,» with additional care provided by a heart team that includes a cardiac surgeon, interventional cardiologist, interventional echocardiographer.

The new document is generally consistent with a Consensus Statement from the American Association for Thoracic Surgery, the American College of Cardiology (ACC), the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons published in December 2019 and covered then by theheart.org / Medscape Cardiology.

In anticipation the CMS coverage proposal, the ACC earlier this year published a Focused Update of the 2017 Expert Consensus Decision Pathway on the Management of Mitral Regurgitation to reflect new evidence in the field, mainly the recent clinical trial data on functional MR from the MITRA-FR and COAPT trials.

“The proposed criteria are nicely guided by the multisociety consensus document, which sought to foster optimal patient outcomes while also maintaining access to TEER,” Sammy Elmariah, MD, MPH, from Massachusetts General Hospital in Boston, commented by email.

“These criteria, in conjunction with results of the COAPT trial, establish TEER as the standard of care for patients with symptomatic functional MR despite guideline-directed medical therapy who do not possess an alternative indication for cardiac surgery,” said Elmariah, a coauthor on both the Consensus Statement and the Focused Update.

The proposed NCD seems “reasonable,” cardiothoracic surgeon Michael J. Reardon, MD, Houston Methodist Hospital, said by email. But he thought there might be some objections to the requirement for TEER centers to have a surgery program with a minimum annual volume for mitral-valve surgeries.

The proposed NCD says a hospital must have “a surgical program that performs ≥25 total mitral valve surgical procedures for severe MR per year, of which at least 10 must be mitral valve repairs.”

“There is a very definite relationship between mitral valve surgery volume and surgical outcomes and between TEER volume and TEER outcomes, but no real relationship between mitral valve surgery volumes and TEER outcomes,” Reardon said. “A mitral valve surgery program is important, but how many cases do you need to be able to start and run a TEER program?”

Edwards Lifesciences is currently testing its own device for TEER: the PASCAL transcatheter mitral valve repair system. Early findings from the company’s ongoing CLASP IID trial, a head-to-head comparison of Pascal and MitraClip, are expected in December 2023.

CMS is seeking comments on the proposed national coverage determination, and will render a final decision within 60 days of the end of the 30-day public comment period.

Elmariah discloses receiving research grants from the American Heart Association, the National Institutes of Health, Edwards Lifesciences, Svelte Medical, and Medtronic, and consulting fees from AstraZeneca. Reardon recently reported no relevant conflicts of interest.

This article first appeared on Medscape.com.

If either high sensitivity cardiac troponin (hs-cTnT) or coronary artery calcium (CAC) are elevated, the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) climbs substantially, which suggests these biomarkers yield more prognostic information when they are used together, according to a cohort study with a median 15 years of follow-up.

Among those with a double negative result, meaning hs-cTnT was less than the limit of detection (<3 ng/L) and the CAC score was zero, only 2.8% developed ASCVD within 10 years, but the rates climbed to 4.6% if hs-cTnT was detectable and to 9.8% if the CAC score exceeded zero even when the other biomarker was negative.

“The increased risk for ASCVD among those with discordant results indicate that their prognostic information is complementary, favoring their conjoined use for risk prediction,” reported a multicenter team of investigators led by Allan S. Jaffe, MD, professor of laboratory medicine and pathology, Mayo Clinic, Rochester, Minn.

The study was performed with data from 6,749 participants in the Multi-Ethnic Study of Atherosclerosis (MESA), which is a longitudinal, community-based study funded by the National Heart, Lung, and Blood Institute. Over the course of long-term follow-up in a patient population that was about half female, 39% non-Hispanic white, 28% Black, 22% Hispanic American, and 12% Asian, ASCVD events were evaluated in relation to both biomarkers measured at baseline.

At baseline, both biomarkers were negative in 22%, both positive in 40%, and discordant in 38%.

After a median follow-up of 15 years, when 1,002 ASCVD events had occurred, the crude rate of ASCVD was 2.8 per 1,000 person-years in the double-negative group. When compared with this, the adjusted hazard ratio for ASCVD among those with double positive biomarkers was 3.5 (P < .00001). Increased risk was also highly significant if just hs-cTnT was positive (HR, 1.59; P = .003) or if just CAC was positive (HR, 2.74; P < .00001).

The added value of using both biomarkers to identify individuals at very low risk of ASCVD makes sense, according to the authors of an accompanying editorial. Written by a team led by John W. McEvoy, MB, BCh, National University of Ireland, Galway, the editorial explained why the information is complementary.

“CAC indicates subclinical atherosclerosis, whereas hs-cTnT indicates myocardial ischemia or damage, not just from coronary stenosis but also due to other conditions like hypertensive heart and left ventricular hypertrophy,” the authors stated.

Although they maintained that adding N-terminal pro-brain natriuretic peptide, which could be drawn from the same blood sample as hs-cTnT, might prove to be an even better but still simple strategy to identify low-risk patients, they praised the concept of combining biomarkers.

“If one’s wish is to identify truly low-risk individuals, then it appears that it takes two negative ASCVD biomarkers to make that wish come true,” the authors of the editorial concluded.

Relative to alternative methods of ASCVD risk assessment, measurement of these biomarkers might be useful for sparing patients from interventions, such as lipid lowering with statin therapy, being considered on the basis of conventional risk factors alone.

Dr. Jaffe said in an interview that he considers the two-biomarker assessment to be a useful tool in the low-risk population that he studied, but he does not consider this strategy as a substitute for other methods, such as those outline in the 2019 ACC/AHA guidelines that address the entire spectrum of risk, although work is planned to see if this approach can be extended to this broader group.*

“The data we have presented now is a good start and suggests that these two objective measures can identify those who are at very low risk and avoid adding individuals who may not be at as low risk if only one of the two tests is used,” Dr. Jaffe explained.

“Given there are now techniques to measure coronary calcium from any chest CT study, and that high sensitivity cardiac troponin is a relatively inexpensive test, putting them together should really help risk stratify patients,” he added.

When asked whether this approach will eventually replace conventional methods of ASCVD risk assessment, such as those proposed in the 2019 American College of Cardiology/American Heart Association guidelines for the primary prevention of cardiovascular disease (Circulation. 2019;140:e596-e646), he said maybe.

“The answer is that we will probe that question in our ongoing studies using continuous data in an attempt to evaluate how to use this approach to risk stratify larger numbers of individuals,” Dr. Jaffe replied.

The senior investigator, Dr. Jaffe, has consulting relationships with many pharmaceutical companies. The editorial authors had no relevant disclosures.

SOURCE: Sandoval Y et al. J Am Coll Cardiol. 2020;76:357-370.

*Correction, 7/27/20: An earlier version of this article mischaracterized Dr. Jaffe's statement.

If either high sensitivity cardiac troponin (hs-cTnT) or coronary artery calcium (CAC) are elevated, the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) climbs substantially, which suggests these biomarkers yield more prognostic information when they are used together, according to a cohort study with a median 15 years of follow-up.

Among those with a double negative result, meaning hs-cTnT was less than the limit of detection (<3 ng/L) and the CAC score was zero, only 2.8% developed ASCVD within 10 years, but the rates climbed to 4.6% if hs-cTnT was detectable and to 9.8% if the CAC score exceeded zero even when the other biomarker was negative.

“The increased risk for ASCVD among those with discordant results indicate that their prognostic information is complementary, favoring their conjoined use for risk prediction,” reported a multicenter team of investigators led by Allan S. Jaffe, MD, professor of laboratory medicine and pathology, Mayo Clinic, Rochester, Minn.

The study was performed with data from 6,749 participants in the Multi-Ethnic Study of Atherosclerosis (MESA), which is a longitudinal, community-based study funded by the National Heart, Lung, and Blood Institute. Over the course of long-term follow-up in a patient population that was about half female, 39% non-Hispanic white, 28% Black, 22% Hispanic American, and 12% Asian, ASCVD events were evaluated in relation to both biomarkers measured at baseline.

At baseline, both biomarkers were negative in 22%, both positive in 40%, and discordant in 38%.

After a median follow-up of 15 years, when 1,002 ASCVD events had occurred, the crude rate of ASCVD was 2.8 per 1,000 person-years in the double-negative group. When compared with this, the adjusted hazard ratio for ASCVD among those with double positive biomarkers was 3.5 (P < .00001). Increased risk was also highly significant if just hs-cTnT was positive (HR, 1.59; P = .003) or if just CAC was positive (HR, 2.74; P < .00001).

The added value of using both biomarkers to identify individuals at very low risk of ASCVD makes sense, according to the authors of an accompanying editorial. Written by a team led by John W. McEvoy, MB, BCh, National University of Ireland, Galway, the editorial explained why the information is complementary.

“CAC indicates subclinical atherosclerosis, whereas hs-cTnT indicates myocardial ischemia or damage, not just from coronary stenosis but also due to other conditions like hypertensive heart and left ventricular hypertrophy,” the authors stated.

Although they maintained that adding N-terminal pro-brain natriuretic peptide, which could be drawn from the same blood sample as hs-cTnT, might prove to be an even better but still simple strategy to identify low-risk patients, they praised the concept of combining biomarkers.

“If one’s wish is to identify truly low-risk individuals, then it appears that it takes two negative ASCVD biomarkers to make that wish come true,” the authors of the editorial concluded.

Relative to alternative methods of ASCVD risk assessment, measurement of these biomarkers might be useful for sparing patients from interventions, such as lipid lowering with statin therapy, being considered on the basis of conventional risk factors alone.

Dr. Jaffe said in an interview that he considers the two-biomarker assessment to be a useful tool in the low-risk population that he studied, but he does not consider this strategy as a substitute for other methods, such as those outline in the 2019 ACC/AHA guidelines that address the entire spectrum of risk, although work is planned to see if this approach can be extended to this broader group.*

“The data we have presented now is a good start and suggests that these two objective measures can identify those who are at very low risk and avoid adding individuals who may not be at as low risk if only one of the two tests is used,” Dr. Jaffe explained.

“Given there are now techniques to measure coronary calcium from any chest CT study, and that high sensitivity cardiac troponin is a relatively inexpensive test, putting them together should really help risk stratify patients,” he added.

When asked whether this approach will eventually replace conventional methods of ASCVD risk assessment, such as those proposed in the 2019 American College of Cardiology/American Heart Association guidelines for the primary prevention of cardiovascular disease (Circulation. 2019;140:e596-e646), he said maybe.

“The answer is that we will probe that question in our ongoing studies using continuous data in an attempt to evaluate how to use this approach to risk stratify larger numbers of individuals,” Dr. Jaffe replied.

The senior investigator, Dr. Jaffe, has consulting relationships with many pharmaceutical companies. The editorial authors had no relevant disclosures.

SOURCE: Sandoval Y et al. J Am Coll Cardiol. 2020;76:357-370.

*Correction, 7/27/20: An earlier version of this article mischaracterized Dr. Jaffe's statement.

If either high sensitivity cardiac troponin (hs-cTnT) or coronary artery calcium (CAC) are elevated, the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) climbs substantially, which suggests these biomarkers yield more prognostic information when they are used together, according to a cohort study with a median 15 years of follow-up.

Among those with a double negative result, meaning hs-cTnT was less than the limit of detection (<3 ng/L) and the CAC score was zero, only 2.8% developed ASCVD within 10 years, but the rates climbed to 4.6% if hs-cTnT was detectable and to 9.8% if the CAC score exceeded zero even when the other biomarker was negative.

“The increased risk for ASCVD among those with discordant results indicate that their prognostic information is complementary, favoring their conjoined use for risk prediction,” reported a multicenter team of investigators led by Allan S. Jaffe, MD, professor of laboratory medicine and pathology, Mayo Clinic, Rochester, Minn.

The study was performed with data from 6,749 participants in the Multi-Ethnic Study of Atherosclerosis (MESA), which is a longitudinal, community-based study funded by the National Heart, Lung, and Blood Institute. Over the course of long-term follow-up in a patient population that was about half female, 39% non-Hispanic white, 28% Black, 22% Hispanic American, and 12% Asian, ASCVD events were evaluated in relation to both biomarkers measured at baseline.

At baseline, both biomarkers were negative in 22%, both positive in 40%, and discordant in 38%.

After a median follow-up of 15 years, when 1,002 ASCVD events had occurred, the crude rate of ASCVD was 2.8 per 1,000 person-years in the double-negative group. When compared with this, the adjusted hazard ratio for ASCVD among those with double positive biomarkers was 3.5 (P < .00001). Increased risk was also highly significant if just hs-cTnT was positive (HR, 1.59; P = .003) or if just CAC was positive (HR, 2.74; P < .00001).

The added value of using both biomarkers to identify individuals at very low risk of ASCVD makes sense, according to the authors of an accompanying editorial. Written by a team led by John W. McEvoy, MB, BCh, National University of Ireland, Galway, the editorial explained why the information is complementary.

“CAC indicates subclinical atherosclerosis, whereas hs-cTnT indicates myocardial ischemia or damage, not just from coronary stenosis but also due to other conditions like hypertensive heart and left ventricular hypertrophy,” the authors stated.

Although they maintained that adding N-terminal pro-brain natriuretic peptide, which could be drawn from the same blood sample as hs-cTnT, might prove to be an even better but still simple strategy to identify low-risk patients, they praised the concept of combining biomarkers.

“If one’s wish is to identify truly low-risk individuals, then it appears that it takes two negative ASCVD biomarkers to make that wish come true,” the authors of the editorial concluded.

Relative to alternative methods of ASCVD risk assessment, measurement of these biomarkers might be useful for sparing patients from interventions, such as lipid lowering with statin therapy, being considered on the basis of conventional risk factors alone.

Dr. Jaffe said in an interview that he considers the two-biomarker assessment to be a useful tool in the low-risk population that he studied, but he does not consider this strategy as a substitute for other methods, such as those outline in the 2019 ACC/AHA guidelines that address the entire spectrum of risk, although work is planned to see if this approach can be extended to this broader group.*

“The data we have presented now is a good start and suggests that these two objective measures can identify those who are at very low risk and avoid adding individuals who may not be at as low risk if only one of the two tests is used,” Dr. Jaffe explained.

“Given there are now techniques to measure coronary calcium from any chest CT study, and that high sensitivity cardiac troponin is a relatively inexpensive test, putting them together should really help risk stratify patients,” he added.

When asked whether this approach will eventually replace conventional methods of ASCVD risk assessment, such as those proposed in the 2019 American College of Cardiology/American Heart Association guidelines for the primary prevention of cardiovascular disease (Circulation. 2019;140:e596-e646), he said maybe.

“The answer is that we will probe that question in our ongoing studies using continuous data in an attempt to evaluate how to use this approach to risk stratify larger numbers of individuals,” Dr. Jaffe replied.

The senior investigator, Dr. Jaffe, has consulting relationships with many pharmaceutical companies. The editorial authors had no relevant disclosures.

SOURCE: Sandoval Y et al. J Am Coll Cardiol. 2020;76:357-370.

*Correction, 7/27/20: An earlier version of this article mischaracterized Dr. Jaffe's statement.

Hospitalists frequently encounter patients with heart failure – a complex, clinical syndrome, which has high prevalence, mortality, hospitalization rates, and health care costs.

The HM20 Virtual session “Updates in Heart Failure” will provide literature updates for all types of heart failure patient scenarios – patients with acute and chronic heart failure, those who are hospitalized with heart failure, and patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). The popular session with questions and answers will be held on Aug. 25.

Presenter Dustin Smith, MD, SFHM, associate professor of medicine in the department of medicine at Emory University, Atlanta, and section chief for education in medical specialty at the Atlanta Veterans Affairs Medical Center, will discuss recent trends, diagnostics, therapeutics, and prognostics for heart failure. He’ll also provide a summary of recent changes to clinical practice guidelines.

“The significance of staying knowledgeable and updated regarding this common admission diagnosis cannot be overstated,” Dr. Smith said. Attendees of this clinical update should learn important practices from new evidence in literature, including an unearthed risk grade predictor of acute heart failure mortality, a diagnostic tool for HFpEF in euvolemic patients with unexplained dyspnea, an examination of the potassium “repletion reflex” in patients hospitalized with heart failure, dietary patterns associated with incident heart failure, and therapies efficacious for HFrEF and/or HFpEF.

“The goal of this session is for attendees to incorporate this new information into their clinical practice so they can optimally manage patients with heart failure,” Dr. Smith said.

The session is specifically curated to impact the clinical practice of hospitalists who provide care for patients with heart failure in the acute care setting and beyond. Key impact areas of clinical practice that will be tackled include:

• Augmenting one’s clinical acumen to diagnose HFpEF.
• Calculating mortality risk for patients with acute heart failure.
• Recognizing other predictors of risk for patients hospitalized with heart failure.
• Recommending dietary, medication, and interventional therapies to prevent future heart failure morbidity and mortality.

Dr. Smith will conclude each literature review with a summary of take-home learning points carefully selected to either change, modify, or confirm the current practice and teaching for providers who care for heart failure patients.

Although Dr. Smith has presented the “Updates in Heart Failure” session in various educational arenas in the past, this is a new update. He has gained vast experience and expertise in this area from conducting extensive and in-depth literature reviews on managing heart failure while preparing for presentations on this topic.

In addition, Dr. Smith has contributed to original research manuscripts, book chapters, and board review–style exam questions in cardiology – including heart failure – and evidence-based medicine topics as an author and editor. He has also sought out additional training and completed faculty development programs targeted at improving his knowledge and skill set to teach evidence-based clinical practice.

Dr. Smith had no relevant financial conflicts to disclose.
 

Updates in Heart Failure

Live Q&A – Tuesday, Aug. 25 1:00 p.m. to 2:00 p.m.

Hospitalists frequently encounter patients with heart failure – a complex, clinical syndrome, which has high prevalence, mortality, hospitalization rates, and health care costs.

The HM20 Virtual session “Updates in Heart Failure” will provide literature updates for all types of heart failure patient scenarios – patients with acute and chronic heart failure, those who are hospitalized with heart failure, and patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). The popular session with questions and answers will be held on Aug. 25.

Presenter Dustin Smith, MD, SFHM, associate professor of medicine in the department of medicine at Emory University, Atlanta, and section chief for education in medical specialty at the Atlanta Veterans Affairs Medical Center, will discuss recent trends, diagnostics, therapeutics, and prognostics for heart failure. He’ll also provide a summary of recent changes to clinical practice guidelines.

“The significance of staying knowledgeable and updated regarding this common admission diagnosis cannot be overstated,” Dr. Smith said. Attendees of this clinical update should learn important practices from new evidence in literature, including an unearthed risk grade predictor of acute heart failure mortality, a diagnostic tool for HFpEF in euvolemic patients with unexplained dyspnea, an examination of the potassium “repletion reflex” in patients hospitalized with heart failure, dietary patterns associated with incident heart failure, and therapies efficacious for HFrEF and/or HFpEF.

“The goal of this session is for attendees to incorporate this new information into their clinical practice so they can optimally manage patients with heart failure,” Dr. Smith said.

The session is specifically curated to impact the clinical practice of hospitalists who provide care for patients with heart failure in the acute care setting and beyond. Key impact areas of clinical practice that will be tackled include:

• Augmenting one’s clinical acumen to diagnose HFpEF.
• Calculating mortality risk for patients with acute heart failure.
• Recognizing other predictors of risk for patients hospitalized with heart failure.
• Recommending dietary, medication, and interventional therapies to prevent future heart failure morbidity and mortality.

Dr. Smith will conclude each literature review with a summary of take-home learning points carefully selected to either change, modify, or confirm the current practice and teaching for providers who care for heart failure patients.

Although Dr. Smith has presented the “Updates in Heart Failure” session in various educational arenas in the past, this is a new update. He has gained vast experience and expertise in this area from conducting extensive and in-depth literature reviews on managing heart failure while preparing for presentations on this topic.

In addition, Dr. Smith has contributed to original research manuscripts, book chapters, and board review–style exam questions in cardiology – including heart failure – and evidence-based medicine topics as an author and editor. He has also sought out additional training and completed faculty development programs targeted at improving his knowledge and skill set to teach evidence-based clinical practice.

Dr. Smith had no relevant financial conflicts to disclose.
 

Updates in Heart Failure

Live Q&A – Tuesday, Aug. 25 1:00 p.m. to 2:00 p.m.

Hospitalists frequently encounter patients with heart failure – a complex, clinical syndrome, which has high prevalence, mortality, hospitalization rates, and health care costs.

The HM20 Virtual session “Updates in Heart Failure” will provide literature updates for all types of heart failure patient scenarios – patients with acute and chronic heart failure, those who are hospitalized with heart failure, and patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). The popular session with questions and answers will be held on Aug. 25.

Presenter Dustin Smith, MD, SFHM, associate professor of medicine in the department of medicine at Emory University, Atlanta, and section chief for education in medical specialty at the Atlanta Veterans Affairs Medical Center, will discuss recent trends, diagnostics, therapeutics, and prognostics for heart failure. He’ll also provide a summary of recent changes to clinical practice guidelines.

“The significance of staying knowledgeable and updated regarding this common admission diagnosis cannot be overstated,” Dr. Smith said. Attendees of this clinical update should learn important practices from new evidence in literature, including an unearthed risk grade predictor of acute heart failure mortality, a diagnostic tool for HFpEF in euvolemic patients with unexplained dyspnea, an examination of the potassium “repletion reflex” in patients hospitalized with heart failure, dietary patterns associated with incident heart failure, and therapies efficacious for HFrEF and/or HFpEF.

“The goal of this session is for attendees to incorporate this new information into their clinical practice so they can optimally manage patients with heart failure,” Dr. Smith said.

The session is specifically curated to impact the clinical practice of hospitalists who provide care for patients with heart failure in the acute care setting and beyond. Key impact areas of clinical practice that will be tackled include:

• Augmenting one’s clinical acumen to diagnose HFpEF.
• Calculating mortality risk for patients with acute heart failure.
• Recognizing other predictors of risk for patients hospitalized with heart failure.
• Recommending dietary, medication, and interventional therapies to prevent future heart failure morbidity and mortality.

Dr. Smith will conclude each literature review with a summary of take-home learning points carefully selected to either change, modify, or confirm the current practice and teaching for providers who care for heart failure patients.

Although Dr. Smith has presented the “Updates in Heart Failure” session in various educational arenas in the past, this is a new update. He has gained vast experience and expertise in this area from conducting extensive and in-depth literature reviews on managing heart failure while preparing for presentations on this topic.

In addition, Dr. Smith has contributed to original research manuscripts, book chapters, and board review–style exam questions in cardiology – including heart failure – and evidence-based medicine topics as an author and editor. He has also sought out additional training and completed faculty development programs targeted at improving his knowledge and skill set to teach evidence-based clinical practice.

Dr. Smith had no relevant financial conflicts to disclose.
 

Updates in Heart Failure

Live Q&A – Tuesday, Aug. 25 1:00 p.m. to 2:00 p.m.

EVIDENCE SUMMARY

A double-blind, double-dummy, placebo-controlled RCT comparing a combination of clopidogrel, aspirin, and omeprazole with clopidogrel, aspirin, and placebo found no increase in composite CV outcomes with the PPI (TABLE).¹ Using a PPI did, however, significantly reduce gastrointestinal (GI) bleeding (hazard ratio [HR] = 0.13; 95% confidence interval [CI], 0.03-0.56).Although several meta-analyses have been conducted, they all rely on this single RCT that directly addresses the question, plus post-hoc analyses of other RCTs.

Four of 5 analyses find little or no difference in CV outcomes with a PPI

Four of 5 posthoc analyses (which weren’t themselves randomized) of RCTs found unclear or no differences in composite CV outcomes with concurrent use of a PPI and antiplatelet therapy, after multivariate adjustment for differences in populations taking or not taking a PPI.

Posthoc analysis of the largest study found worse CV outcomes for both clopidogrel and ticagrelor with concomitant PPI use.² However, patients on any GI drugs (PPI or non-PPI) had composite outcomes similar to patients on a PPI (PPI vs non-PPI GI treatment: HR = 0.98; 95% CI, 0.79-1.23), and patients not taking GI drugs had fewer composite outcomes compared with patients on a PPI (clopidogrel vs no GI therapy: HR = 1.29; 95% CI, 1.12-1.49; ticagrelor vs no GI therapy: HR = 1.30; 95% CI, 1.14-1.49). Researchers postulated that because the rate of composite outcomes increased equally for patients on any GI drug, the higher rate of CV adverse events with a PPI might have been related to GI disease rather than PPI use.

A similar posthoc analysis found no differences with or without PPI use among patients with ACS undergoing planned percutaneous coronary intervention (PCI) and assigned to clopidogrel or prasugrel.³ Researchers performed multivariate adjustment for differences in age, gender, ethnicity, and initial presence of unstable angina/non-ST-elevation MI.

A smaller study also found no significant differences in composite CV outcomes in patients using PPIs.⁴ Patients did have higher rates of MI (HR = 0.62; 95% CI, 0.42-0.91), but they were more likely to be older and have a previous diagnosis of non-ST-elevation MI, higher incidence of previous coronary artery bypass graft surgery, and history of peptic ulcer disease.

The fourth posthoc analysis of an RCT found that concomitant PPI use (91% of patients on lansoprazole) didn’t alter outcomes among patients undergoing PCI and receiving dual antiplatelet therapy with clopidogrel and aspirin.⁵ Researchers used a multivariate adjustment for differences in age, gender, and renal function and found no difference in outcomes during the 6-month or 24-month period. PPI prescription was at physician discretion. Researchers didn’t assess for dose-dependent effects of PPI.

A fifth, flawed study finds more adverse events with PPIs

A posthoc analysis of a smaller, open-label trial found increased major adverse cardiac events with PPI use among patients taking clopidogrel after PCI.⁶ Researchers didn’t adjust for differences in populations at baseline, however, and patients taking PPIs were more likely to be female or older and have diabetes, GI disease, or higher serum creatinine levels.

Continue to: Editor's takeaway

 

 

Editor’s takeaway

The best evidence (a large RCT) found that adding a PPI to antiplatelet therapy didn’t alter CV outcomes in patients with ACS, but it did reduce GI bleeds. Hopefully this will give providers the confidence to use PPIs, if clinically indicated, in patients taking antiplatelet therapy with clopidogrel or prasugrel.

EVIDENCE SUMMARY

A double-blind, double-dummy, placebo-controlled RCT comparing a combination of clopidogrel, aspirin, and omeprazole with clopidogrel, aspirin, and placebo found no increase in composite CV outcomes with the PPI (TABLE).¹ Using a PPI did, however, significantly reduce gastrointestinal (GI) bleeding (hazard ratio [HR] = 0.13; 95% confidence interval [CI], 0.03-0.56).Although several meta-analyses have been conducted, they all rely on this single RCT that directly addresses the question, plus post-hoc analyses of other RCTs.

Four of 5 analyses find little or no difference in CV outcomes with a PPI

Four of 5 posthoc analyses (which weren’t themselves randomized) of RCTs found unclear or no differences in composite CV outcomes with concurrent use of a PPI and antiplatelet therapy, after multivariate adjustment for differences in populations taking or not taking a PPI.

Posthoc analysis of the largest study found worse CV outcomes for both clopidogrel and ticagrelor with concomitant PPI use.² However, patients on any GI drugs (PPI or non-PPI) had composite outcomes similar to patients on a PPI (PPI vs non-PPI GI treatment: HR = 0.98; 95% CI, 0.79-1.23), and patients not taking GI drugs had fewer composite outcomes compared with patients on a PPI (clopidogrel vs no GI therapy: HR = 1.29; 95% CI, 1.12-1.49; ticagrelor vs no GI therapy: HR = 1.30; 95% CI, 1.14-1.49). Researchers postulated that because the rate of composite outcomes increased equally for patients on any GI drug, the higher rate of CV adverse events with a PPI might have been related to GI disease rather than PPI use.

A similar posthoc analysis found no differences with or without PPI use among patients with ACS undergoing planned percutaneous coronary intervention (PCI) and assigned to clopidogrel or prasugrel.³ Researchers performed multivariate adjustment for differences in age, gender, ethnicity, and initial presence of unstable angina/non-ST-elevation MI.

A smaller study also found no significant differences in composite CV outcomes in patients using PPIs.⁴ Patients did have higher rates of MI (HR = 0.62; 95% CI, 0.42-0.91), but they were more likely to be older and have a previous diagnosis of non-ST-elevation MI, higher incidence of previous coronary artery bypass graft surgery, and history of peptic ulcer disease.

The fourth posthoc analysis of an RCT found that concomitant PPI use (91% of patients on lansoprazole) didn’t alter outcomes among patients undergoing PCI and receiving dual antiplatelet therapy with clopidogrel and aspirin.⁵ Researchers used a multivariate adjustment for differences in age, gender, and renal function and found no difference in outcomes during the 6-month or 24-month period. PPI prescription was at physician discretion. Researchers didn’t assess for dose-dependent effects of PPI.

A fifth, flawed study finds more adverse events with PPIs

A posthoc analysis of a smaller, open-label trial found increased major adverse cardiac events with PPI use among patients taking clopidogrel after PCI.⁶ Researchers didn’t adjust for differences in populations at baseline, however, and patients taking PPIs were more likely to be female or older and have diabetes, GI disease, or higher serum creatinine levels.

Continue to: Editor's takeaway

 

 

Editor’s takeaway

The best evidence (a large RCT) found that adding a PPI to antiplatelet therapy didn’t alter CV outcomes in patients with ACS, but it did reduce GI bleeds. Hopefully this will give providers the confidence to use PPIs, if clinically indicated, in patients taking antiplatelet therapy with clopidogrel or prasugrel.

EVIDENCE SUMMARY

A double-blind, double-dummy, placebo-controlled RCT comparing a combination of clopidogrel, aspirin, and omeprazole with clopidogrel, aspirin, and placebo found no increase in composite CV outcomes with the PPI (TABLE).¹ Using a PPI did, however, significantly reduce gastrointestinal (GI) bleeding (hazard ratio [HR] = 0.13; 95% confidence interval [CI], 0.03-0.56).Although several meta-analyses have been conducted, they all rely on this single RCT that directly addresses the question, plus post-hoc analyses of other RCTs.

Four of 5 analyses find little or no difference in CV outcomes with a PPI

Four of 5 posthoc analyses (which weren’t themselves randomized) of RCTs found unclear or no differences in composite CV outcomes with concurrent use of a PPI and antiplatelet therapy, after multivariate adjustment for differences in populations taking or not taking a PPI.

Posthoc analysis of the largest study found worse CV outcomes for both clopidogrel and ticagrelor with concomitant PPI use.² However, patients on any GI drugs (PPI or non-PPI) had composite outcomes similar to patients on a PPI (PPI vs non-PPI GI treatment: HR = 0.98; 95% CI, 0.79-1.23), and patients not taking GI drugs had fewer composite outcomes compared with patients on a PPI (clopidogrel vs no GI therapy: HR = 1.29; 95% CI, 1.12-1.49; ticagrelor vs no GI therapy: HR = 1.30; 95% CI, 1.14-1.49). Researchers postulated that because the rate of composite outcomes increased equally for patients on any GI drug, the higher rate of CV adverse events with a PPI might have been related to GI disease rather than PPI use.

A similar posthoc analysis found no differences with or without PPI use among patients with ACS undergoing planned percutaneous coronary intervention (PCI) and assigned to clopidogrel or prasugrel.³ Researchers performed multivariate adjustment for differences in age, gender, ethnicity, and initial presence of unstable angina/non-ST-elevation MI.

A smaller study also found no significant differences in composite CV outcomes in patients using PPIs.⁴ Patients did have higher rates of MI (HR = 0.62; 95% CI, 0.42-0.91), but they were more likely to be older and have a previous diagnosis of non-ST-elevation MI, higher incidence of previous coronary artery bypass graft surgery, and history of peptic ulcer disease.

The fourth posthoc analysis of an RCT found that concomitant PPI use (91% of patients on lansoprazole) didn’t alter outcomes among patients undergoing PCI and receiving dual antiplatelet therapy with clopidogrel and aspirin.⁵ Researchers used a multivariate adjustment for differences in age, gender, and renal function and found no difference in outcomes during the 6-month or 24-month period. PPI prescription was at physician discretion. Researchers didn’t assess for dose-dependent effects of PPI.

A fifth, flawed study finds more adverse events with PPIs

A posthoc analysis of a smaller, open-label trial found increased major adverse cardiac events with PPI use among patients taking clopidogrel after PCI.⁶ Researchers didn’t adjust for differences in populations at baseline, however, and patients taking PPIs were more likely to be female or older and have diabetes, GI disease, or higher serum creatinine levels.

Continue to: Editor's takeaway

 

 

Editor’s takeaway

The best evidence (a large RCT) found that adding a PPI to antiplatelet therapy didn’t alter CV outcomes in patients with ACS, but it did reduce GI bleeds. Hopefully this will give providers the confidence to use PPIs, if clinically indicated, in patients taking antiplatelet therapy with clopidogrel or prasugrel.