User login
Food insecurity a growing problem for many with CVD
A growing number of Americans with cardiovascular disease (CVD) have limited or uncertain access to food, results of a new study suggest.
An analysis of data from the National Health and Nutrition Examination Survey (NHANES) representing more than 300 million American adults found that, overall, 38.1% of people with cardiovascular disease were food insecure in 2017-2019.
Twenty years earlier, that rate was 16.3%.
“What really stood out from our study is how frequent food insecurity is among people with cardiovascular disease, compared to those without cardiovascular disease,” lead author, Eric J. Brandt, MD, MHS, a cardiologist at the University of Michigan Health Frankel Cardiovascular Center, Ann Arbor, said in an interview.
“We believe that the relationship between food insecurity and cardiovascular disease is bidirectional. Food insecurity puts people at risk for cardiovascular disease, which then makes them vulnerable to events like myocardial infarction or stroke, which in turn may make them less able to work, thereby worsening their financial situation and increasing their vulnerability to food insecurity,” Dr. Brandt said.
For the analysis, Dr. Brandt and his team used an analytic sample of 57,517 adults to represent 312 million non-institutionalized adults in the United States.
Overall, 6,770 individuals (11.8%) in the analytic sample reported food insecurity.
Food insecurity was more prevalent among Hispanic people (n = 1,938, 24.0%) and non-Hispanic Black people (n = 1,202, 18.2%), compared with non-Hispanic Asian people (n = 100, 8.0%), and non-Hispanic White people (n = 3,221, 8.5%).
The prevalence of cardiovascular disease in the sample was 7.9% (n = 4,527).
Hypertension was the most prevalent CVD risk factor, reported in 49.6% of the sample. This was followed by obesity in 33.2%, dyslipidemia in 30.8%, and diabetes in 11.2%.
The findings were published online in JAMA Cardiology.
“All cardiovascular disease and cardiometabolic diseases except coronary artery disease were more prevalent among those with food insecurity,” Dr. Brandt noted.
“The results of our study are especially timely, as the White House just hosted its first conference on Hunger, Nutrition, and Health in over 50 years. Food insecurity is a focus of that conference. In the last few years, especially in relation to the pandemic, there has been expansion of some of the federal programs to prevent food insecurity. I would like to see a continued effort to solve this,” he said.
Dr. Brandt added that he hopes clinicians will be more cognizant of the problem of food insecurity and other social determinants of health when they see their patients.
“If someone is not going to be able to afford the food on their table, they’re probably not going to pay for their medications. Recognizing these social determinants in the clinical setting and helping our patients access local resources may address the underlying factors contributing to heart disease,” he said.
Uphill battle
Johanna Contreras, MD, advanced heart failure and transplant cardiologist at the Mount Sinai Hospital, New York, treats food insecure cardiovascular patients in her practice and tries to educate them about good nutrition. But it is an uphill battle.
“A lot of my patients live in the South Bronx. They have hypertension, hypercholesterolemia, and there are no grocery stores where they can buy fresh vegetables. I talk to them about eating healthy. They tell me it’s impossible. The stores only have pre-packaged foods. So even in the South Bronx, even though it is in New York, it is very hard to get fresh food. And when it is available, it is very expensive,” Dr. Contreras told this news organization.
“Fresh pineapples can cost $8. A fast-food burger costs $3. So that is what they buy: It’s what they can afford. Even the store managers don’t want to stock fresh produce because it can spoil. They open stores, like Whole Foods, but in the more affluent neighborhoods. They should open one in poor neighborhoods,” she said.
Dr. Contreras says she spends much of her time educating her patients about good nutrition. She asks them to keep a food diary and analyzes the results at each visit.
“I look at what they eat, and I try to see how I can use this information in a good way. I advise them to use frozen foods, and avoid canned, because it is a lot healthier. I am pragmatic, because I know that if I tell my patients to eat salmon, for example, they aren’t going to be able to afford it, if they can even access it.”
She also informs them about relatively healthy fast-food choices.
“I tell them to order 100% fruit juice, water, or milk when they go to McDonalds or other fast-food places. So I think this study is very important. Food insecurity is a very important component of cardiovascular disease, and unfortunately, minority communities are where this occurs.”
Dr. Brandt and Dr. Contreras report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A growing number of Americans with cardiovascular disease (CVD) have limited or uncertain access to food, results of a new study suggest.
An analysis of data from the National Health and Nutrition Examination Survey (NHANES) representing more than 300 million American adults found that, overall, 38.1% of people with cardiovascular disease were food insecure in 2017-2019.
Twenty years earlier, that rate was 16.3%.
“What really stood out from our study is how frequent food insecurity is among people with cardiovascular disease, compared to those without cardiovascular disease,” lead author, Eric J. Brandt, MD, MHS, a cardiologist at the University of Michigan Health Frankel Cardiovascular Center, Ann Arbor, said in an interview.
“We believe that the relationship between food insecurity and cardiovascular disease is bidirectional. Food insecurity puts people at risk for cardiovascular disease, which then makes them vulnerable to events like myocardial infarction or stroke, which in turn may make them less able to work, thereby worsening their financial situation and increasing their vulnerability to food insecurity,” Dr. Brandt said.
For the analysis, Dr. Brandt and his team used an analytic sample of 57,517 adults to represent 312 million non-institutionalized adults in the United States.
Overall, 6,770 individuals (11.8%) in the analytic sample reported food insecurity.
Food insecurity was more prevalent among Hispanic people (n = 1,938, 24.0%) and non-Hispanic Black people (n = 1,202, 18.2%), compared with non-Hispanic Asian people (n = 100, 8.0%), and non-Hispanic White people (n = 3,221, 8.5%).
The prevalence of cardiovascular disease in the sample was 7.9% (n = 4,527).
Hypertension was the most prevalent CVD risk factor, reported in 49.6% of the sample. This was followed by obesity in 33.2%, dyslipidemia in 30.8%, and diabetes in 11.2%.
The findings were published online in JAMA Cardiology.
“All cardiovascular disease and cardiometabolic diseases except coronary artery disease were more prevalent among those with food insecurity,” Dr. Brandt noted.
“The results of our study are especially timely, as the White House just hosted its first conference on Hunger, Nutrition, and Health in over 50 years. Food insecurity is a focus of that conference. In the last few years, especially in relation to the pandemic, there has been expansion of some of the federal programs to prevent food insecurity. I would like to see a continued effort to solve this,” he said.
Dr. Brandt added that he hopes clinicians will be more cognizant of the problem of food insecurity and other social determinants of health when they see their patients.
“If someone is not going to be able to afford the food on their table, they’re probably not going to pay for their medications. Recognizing these social determinants in the clinical setting and helping our patients access local resources may address the underlying factors contributing to heart disease,” he said.
Uphill battle
Johanna Contreras, MD, advanced heart failure and transplant cardiologist at the Mount Sinai Hospital, New York, treats food insecure cardiovascular patients in her practice and tries to educate them about good nutrition. But it is an uphill battle.
“A lot of my patients live in the South Bronx. They have hypertension, hypercholesterolemia, and there are no grocery stores where they can buy fresh vegetables. I talk to them about eating healthy. They tell me it’s impossible. The stores only have pre-packaged foods. So even in the South Bronx, even though it is in New York, it is very hard to get fresh food. And when it is available, it is very expensive,” Dr. Contreras told this news organization.
“Fresh pineapples can cost $8. A fast-food burger costs $3. So that is what they buy: It’s what they can afford. Even the store managers don’t want to stock fresh produce because it can spoil. They open stores, like Whole Foods, but in the more affluent neighborhoods. They should open one in poor neighborhoods,” she said.
Dr. Contreras says she spends much of her time educating her patients about good nutrition. She asks them to keep a food diary and analyzes the results at each visit.
“I look at what they eat, and I try to see how I can use this information in a good way. I advise them to use frozen foods, and avoid canned, because it is a lot healthier. I am pragmatic, because I know that if I tell my patients to eat salmon, for example, they aren’t going to be able to afford it, if they can even access it.”
She also informs them about relatively healthy fast-food choices.
“I tell them to order 100% fruit juice, water, or milk when they go to McDonalds or other fast-food places. So I think this study is very important. Food insecurity is a very important component of cardiovascular disease, and unfortunately, minority communities are where this occurs.”
Dr. Brandt and Dr. Contreras report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A growing number of Americans with cardiovascular disease (CVD) have limited or uncertain access to food, results of a new study suggest.
An analysis of data from the National Health and Nutrition Examination Survey (NHANES) representing more than 300 million American adults found that, overall, 38.1% of people with cardiovascular disease were food insecure in 2017-2019.
Twenty years earlier, that rate was 16.3%.
“What really stood out from our study is how frequent food insecurity is among people with cardiovascular disease, compared to those without cardiovascular disease,” lead author, Eric J. Brandt, MD, MHS, a cardiologist at the University of Michigan Health Frankel Cardiovascular Center, Ann Arbor, said in an interview.
“We believe that the relationship between food insecurity and cardiovascular disease is bidirectional. Food insecurity puts people at risk for cardiovascular disease, which then makes them vulnerable to events like myocardial infarction or stroke, which in turn may make them less able to work, thereby worsening their financial situation and increasing their vulnerability to food insecurity,” Dr. Brandt said.
For the analysis, Dr. Brandt and his team used an analytic sample of 57,517 adults to represent 312 million non-institutionalized adults in the United States.
Overall, 6,770 individuals (11.8%) in the analytic sample reported food insecurity.
Food insecurity was more prevalent among Hispanic people (n = 1,938, 24.0%) and non-Hispanic Black people (n = 1,202, 18.2%), compared with non-Hispanic Asian people (n = 100, 8.0%), and non-Hispanic White people (n = 3,221, 8.5%).
The prevalence of cardiovascular disease in the sample was 7.9% (n = 4,527).
Hypertension was the most prevalent CVD risk factor, reported in 49.6% of the sample. This was followed by obesity in 33.2%, dyslipidemia in 30.8%, and diabetes in 11.2%.
The findings were published online in JAMA Cardiology.
“All cardiovascular disease and cardiometabolic diseases except coronary artery disease were more prevalent among those with food insecurity,” Dr. Brandt noted.
“The results of our study are especially timely, as the White House just hosted its first conference on Hunger, Nutrition, and Health in over 50 years. Food insecurity is a focus of that conference. In the last few years, especially in relation to the pandemic, there has been expansion of some of the federal programs to prevent food insecurity. I would like to see a continued effort to solve this,” he said.
Dr. Brandt added that he hopes clinicians will be more cognizant of the problem of food insecurity and other social determinants of health when they see their patients.
“If someone is not going to be able to afford the food on their table, they’re probably not going to pay for their medications. Recognizing these social determinants in the clinical setting and helping our patients access local resources may address the underlying factors contributing to heart disease,” he said.
Uphill battle
Johanna Contreras, MD, advanced heart failure and transplant cardiologist at the Mount Sinai Hospital, New York, treats food insecure cardiovascular patients in her practice and tries to educate them about good nutrition. But it is an uphill battle.
“A lot of my patients live in the South Bronx. They have hypertension, hypercholesterolemia, and there are no grocery stores where they can buy fresh vegetables. I talk to them about eating healthy. They tell me it’s impossible. The stores only have pre-packaged foods. So even in the South Bronx, even though it is in New York, it is very hard to get fresh food. And when it is available, it is very expensive,” Dr. Contreras told this news organization.
“Fresh pineapples can cost $8. A fast-food burger costs $3. So that is what they buy: It’s what they can afford. Even the store managers don’t want to stock fresh produce because it can spoil. They open stores, like Whole Foods, but in the more affluent neighborhoods. They should open one in poor neighborhoods,” she said.
Dr. Contreras says she spends much of her time educating her patients about good nutrition. She asks them to keep a food diary and analyzes the results at each visit.
“I look at what they eat, and I try to see how I can use this information in a good way. I advise them to use frozen foods, and avoid canned, because it is a lot healthier. I am pragmatic, because I know that if I tell my patients to eat salmon, for example, they aren’t going to be able to afford it, if they can even access it.”
She also informs them about relatively healthy fast-food choices.
“I tell them to order 100% fruit juice, water, or milk when they go to McDonalds or other fast-food places. So I think this study is very important. Food insecurity is a very important component of cardiovascular disease, and unfortunately, minority communities are where this occurs.”
Dr. Brandt and Dr. Contreras report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SMART-CHOICE 3-year results support dropping aspirin after PCI
Shortening the duration of dual-antiplatelet therapy (DAPT) and continuing with a P2Y12 inhibitor alone after percutaneous coronary intervention (PCI) was associated with a similar rate of ischemic events but with less bleeding than prolonged DAPT after 3 years of follow-up in the SMART-CHOICE trial.
“The current the investigators, with lead author Ki Hong Choi, MD, division of cardiology, department of medicine, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea, conclude.
The 3-year results from the study were published online in JAMA Cardiology.
The authors explain that although dual therapy with aspirin and a P2Y12 inhibitor after PCI with a drug-eluting stent (DES) is crucial to reduce the risk of ischemic events, it raises concerns about increased risk of bleeding, and the antiplatelet strategy after PCI is currently shifting to reduce the duration of DAPT.
Several recent randomized studies have consistently shown that a short duration of DAPT (1-3 months) followed by P2Y12 inhibitor monotherapy had ischemia protection effects comparable with that of DAPT of longer duration, and it was associated with a significantly reduced risk of bleeding events in patients who underwent PCI, they note. However, these studies have so far reported only 1-year outcomes, and long-term results are not yet available.
The SMART-CHOICE trial compared two antiplatelet strategies – 3 months of DAPT followed by long-term P2Y12 inhibitor monotherapy (mainly with clopidogrel) or prolonged DAPT for 12 months or longer – in 2,993 patients who had undergone PCI with a drug-eluting stent. Results at 12 months showed a similar rate of ischemic events with both strategies but a lower rate of bleeding in the group that received shortened DAPT.
The SMART-CHOICE investigators now report the 3-year results showing similar outcomes.
At 3 years, the primary endpoint, a composite of all-cause death, myocardial infarction, or stroke, had occurred in 6.3% of the shortened DAPT group and 6.1% in the prolonged DAPT group, giving a hazard ratio of 1.06 (95% confidence interval, 0.79-1.44).
But in the shortened DAPT group, the risk of bleeding was reduced. Bleeding Academic Research Consortium (BARC) types 2-5 bleeding had occurred in 3.2% of the shortened DAPT group and in 8.2% of the prolonged DAPT group (hazard ratio, 0.39; 95% CI, 0.28-0.55). Major bleeding, BARC types 3-5, occurred in 1.2% of the shortened DAPT group and in 2.4% of the prolonged DAPT group (HR, 0.56; 95% CI 0.31-0.99).
The landmark analyses between 3 months and 3 years and per-protocol analyses showed consistent results.
The researchers point out that this is the first trial to report on the long-term safety and efficacy of P2Y12-inhibitor monotherapy as long-term maintenance therapy for stable patients treated with PCI.
“Especially considering that extended DAPT significantly reduced the risks of ischemic events compared with aspirin monotherapy in a couple of trials, comparison between P2Y12-inhibitor monotherapy and prolonged DAPT for recurrent ischemic events over a longer period beyond 1 year is of great importance,” they say.
They cite two other trials – HOST-EXAM and GLOBAL LEADERS – which have shown P2Y12-inhibitor monotherapy to be superior to aspirin monotherapy in preventing both ischemic and bleeding events during the long-term maintenance period after PCI.
“Combining the results of the current study, HOST-EXAM trial, and landmark analysis of the GLOBAL LEADERS trial, long-term P2Y12-inhibitor monotherapy after a minimum period of DAPT might be the most reliable option from among aspirin monotherapy, P2Y12 monotherapy, and extended DAPT for maintenance therapy after stabilizing patients who have undergone PCI with a current-generation DES,” they conclude.
They note that the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions guidelines for coronary artery revascularization newly recommends a shorter course of DAPT followed by P2Y12 monotherapy as a class IIa indication. The recommendation is based on results of five large, randomized clinical trials, including SMART-CHOICE, TWILIGHT, STOPDAPT-2, TICO, and GLOBAL LEADERS.
“The current results of extended follow-up from the SMART-CHOICE trial support evidence of aspirin-dropping strategy with indefinite use of P2Y12 inhibitor after minimum use of DAPT in patients who underwent PCI,” they say.
They point out that two further trials, A-CLOSE in high-risk patients and SMART-CHOICE III, will be helpful to confirm these findings.
P2Y12-inhibitor monotherapy ‘attractive concept’
In an accompanying editor’s note, Ajay Kirtane, MD, Columbia University Irving Medical Center/New York–Presbyterian Hospital, New York, and Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai and the Cardiovascular Research Foundation, New York, note that current guidelines recommend 3-6 months of DAPT following PCI with current-generation drug-eluting stents in stable patients and 6-12 months or longer for those with acute coronary syndromes. For patients at higher risk of bleeding, even shorter DAPT durations can be considered on a case-by-case basis.
Historically, the component of DAPT subject to discontinuation decisions was the P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor), but more recent trials have further explored whether discontinuation of the aspirin component of DAPT can mitigate bleeding while preserving anti-ischemic efficacy.
The editorialists explain that the concept of P2Y1-inhibitor monotherapy is attractive because it may optimize antiplatelet effects through a single agent that can avoid the gastrointestinal toxicity of aspirin as well as the increased bleeding that comes with combing multiple antithrombotic agents.
They suggest that the long-term results from the SMART-CHOICE trial “should lead clinicians to consider a strategy of monotherapy after a short period of DAPT as a viable one to mitigate bleeding risk,” although they also point out that SMART-CHOICE was underpowered to rigorously assess ischemic differences, so caution is warranted.
“For patients at greatest risk for recurrent ischemic events, the role of continued DAPT is always an option, but these data (and other consistent trials) give clinicians more options to pursue individualized treatment decisions,” they write.
“To some, the continually moving field of post-PCI antiplatelet therapy has provided too many choices, which can at times be dizzying. To us, every patient is different, and thoughtful evidence-based consideration is increasingly possible for many of our treatment decisions,” they conclude.
The SMART-CHOICE study was supported by unrestricted grants from the Korean Society of Interventional Cardiology, Abbott Vascular, Biotronik, and Boston Scientific.
A version of this article first appeared on Medscape.com.
Shortening the duration of dual-antiplatelet therapy (DAPT) and continuing with a P2Y12 inhibitor alone after percutaneous coronary intervention (PCI) was associated with a similar rate of ischemic events but with less bleeding than prolonged DAPT after 3 years of follow-up in the SMART-CHOICE trial.
“The current the investigators, with lead author Ki Hong Choi, MD, division of cardiology, department of medicine, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea, conclude.
The 3-year results from the study were published online in JAMA Cardiology.
The authors explain that although dual therapy with aspirin and a P2Y12 inhibitor after PCI with a drug-eluting stent (DES) is crucial to reduce the risk of ischemic events, it raises concerns about increased risk of bleeding, and the antiplatelet strategy after PCI is currently shifting to reduce the duration of DAPT.
Several recent randomized studies have consistently shown that a short duration of DAPT (1-3 months) followed by P2Y12 inhibitor monotherapy had ischemia protection effects comparable with that of DAPT of longer duration, and it was associated with a significantly reduced risk of bleeding events in patients who underwent PCI, they note. However, these studies have so far reported only 1-year outcomes, and long-term results are not yet available.
The SMART-CHOICE trial compared two antiplatelet strategies – 3 months of DAPT followed by long-term P2Y12 inhibitor monotherapy (mainly with clopidogrel) or prolonged DAPT for 12 months or longer – in 2,993 patients who had undergone PCI with a drug-eluting stent. Results at 12 months showed a similar rate of ischemic events with both strategies but a lower rate of bleeding in the group that received shortened DAPT.
The SMART-CHOICE investigators now report the 3-year results showing similar outcomes.
At 3 years, the primary endpoint, a composite of all-cause death, myocardial infarction, or stroke, had occurred in 6.3% of the shortened DAPT group and 6.1% in the prolonged DAPT group, giving a hazard ratio of 1.06 (95% confidence interval, 0.79-1.44).
But in the shortened DAPT group, the risk of bleeding was reduced. Bleeding Academic Research Consortium (BARC) types 2-5 bleeding had occurred in 3.2% of the shortened DAPT group and in 8.2% of the prolonged DAPT group (hazard ratio, 0.39; 95% CI, 0.28-0.55). Major bleeding, BARC types 3-5, occurred in 1.2% of the shortened DAPT group and in 2.4% of the prolonged DAPT group (HR, 0.56; 95% CI 0.31-0.99).
The landmark analyses between 3 months and 3 years and per-protocol analyses showed consistent results.
The researchers point out that this is the first trial to report on the long-term safety and efficacy of P2Y12-inhibitor monotherapy as long-term maintenance therapy for stable patients treated with PCI.
“Especially considering that extended DAPT significantly reduced the risks of ischemic events compared with aspirin monotherapy in a couple of trials, comparison between P2Y12-inhibitor monotherapy and prolonged DAPT for recurrent ischemic events over a longer period beyond 1 year is of great importance,” they say.
They cite two other trials – HOST-EXAM and GLOBAL LEADERS – which have shown P2Y12-inhibitor monotherapy to be superior to aspirin monotherapy in preventing both ischemic and bleeding events during the long-term maintenance period after PCI.
“Combining the results of the current study, HOST-EXAM trial, and landmark analysis of the GLOBAL LEADERS trial, long-term P2Y12-inhibitor monotherapy after a minimum period of DAPT might be the most reliable option from among aspirin monotherapy, P2Y12 monotherapy, and extended DAPT for maintenance therapy after stabilizing patients who have undergone PCI with a current-generation DES,” they conclude.
They note that the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions guidelines for coronary artery revascularization newly recommends a shorter course of DAPT followed by P2Y12 monotherapy as a class IIa indication. The recommendation is based on results of five large, randomized clinical trials, including SMART-CHOICE, TWILIGHT, STOPDAPT-2, TICO, and GLOBAL LEADERS.
“The current results of extended follow-up from the SMART-CHOICE trial support evidence of aspirin-dropping strategy with indefinite use of P2Y12 inhibitor after minimum use of DAPT in patients who underwent PCI,” they say.
They point out that two further trials, A-CLOSE in high-risk patients and SMART-CHOICE III, will be helpful to confirm these findings.
P2Y12-inhibitor monotherapy ‘attractive concept’
In an accompanying editor’s note, Ajay Kirtane, MD, Columbia University Irving Medical Center/New York–Presbyterian Hospital, New York, and Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai and the Cardiovascular Research Foundation, New York, note that current guidelines recommend 3-6 months of DAPT following PCI with current-generation drug-eluting stents in stable patients and 6-12 months or longer for those with acute coronary syndromes. For patients at higher risk of bleeding, even shorter DAPT durations can be considered on a case-by-case basis.
Historically, the component of DAPT subject to discontinuation decisions was the P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor), but more recent trials have further explored whether discontinuation of the aspirin component of DAPT can mitigate bleeding while preserving anti-ischemic efficacy.
The editorialists explain that the concept of P2Y1-inhibitor monotherapy is attractive because it may optimize antiplatelet effects through a single agent that can avoid the gastrointestinal toxicity of aspirin as well as the increased bleeding that comes with combing multiple antithrombotic agents.
They suggest that the long-term results from the SMART-CHOICE trial “should lead clinicians to consider a strategy of monotherapy after a short period of DAPT as a viable one to mitigate bleeding risk,” although they also point out that SMART-CHOICE was underpowered to rigorously assess ischemic differences, so caution is warranted.
“For patients at greatest risk for recurrent ischemic events, the role of continued DAPT is always an option, but these data (and other consistent trials) give clinicians more options to pursue individualized treatment decisions,” they write.
“To some, the continually moving field of post-PCI antiplatelet therapy has provided too many choices, which can at times be dizzying. To us, every patient is different, and thoughtful evidence-based consideration is increasingly possible for many of our treatment decisions,” they conclude.
The SMART-CHOICE study was supported by unrestricted grants from the Korean Society of Interventional Cardiology, Abbott Vascular, Biotronik, and Boston Scientific.
A version of this article first appeared on Medscape.com.
Shortening the duration of dual-antiplatelet therapy (DAPT) and continuing with a P2Y12 inhibitor alone after percutaneous coronary intervention (PCI) was associated with a similar rate of ischemic events but with less bleeding than prolonged DAPT after 3 years of follow-up in the SMART-CHOICE trial.
“The current the investigators, with lead author Ki Hong Choi, MD, division of cardiology, department of medicine, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea, conclude.
The 3-year results from the study were published online in JAMA Cardiology.
The authors explain that although dual therapy with aspirin and a P2Y12 inhibitor after PCI with a drug-eluting stent (DES) is crucial to reduce the risk of ischemic events, it raises concerns about increased risk of bleeding, and the antiplatelet strategy after PCI is currently shifting to reduce the duration of DAPT.
Several recent randomized studies have consistently shown that a short duration of DAPT (1-3 months) followed by P2Y12 inhibitor monotherapy had ischemia protection effects comparable with that of DAPT of longer duration, and it was associated with a significantly reduced risk of bleeding events in patients who underwent PCI, they note. However, these studies have so far reported only 1-year outcomes, and long-term results are not yet available.
The SMART-CHOICE trial compared two antiplatelet strategies – 3 months of DAPT followed by long-term P2Y12 inhibitor monotherapy (mainly with clopidogrel) or prolonged DAPT for 12 months or longer – in 2,993 patients who had undergone PCI with a drug-eluting stent. Results at 12 months showed a similar rate of ischemic events with both strategies but a lower rate of bleeding in the group that received shortened DAPT.
The SMART-CHOICE investigators now report the 3-year results showing similar outcomes.
At 3 years, the primary endpoint, a composite of all-cause death, myocardial infarction, or stroke, had occurred in 6.3% of the shortened DAPT group and 6.1% in the prolonged DAPT group, giving a hazard ratio of 1.06 (95% confidence interval, 0.79-1.44).
But in the shortened DAPT group, the risk of bleeding was reduced. Bleeding Academic Research Consortium (BARC) types 2-5 bleeding had occurred in 3.2% of the shortened DAPT group and in 8.2% of the prolonged DAPT group (hazard ratio, 0.39; 95% CI, 0.28-0.55). Major bleeding, BARC types 3-5, occurred in 1.2% of the shortened DAPT group and in 2.4% of the prolonged DAPT group (HR, 0.56; 95% CI 0.31-0.99).
The landmark analyses between 3 months and 3 years and per-protocol analyses showed consistent results.
The researchers point out that this is the first trial to report on the long-term safety and efficacy of P2Y12-inhibitor monotherapy as long-term maintenance therapy for stable patients treated with PCI.
“Especially considering that extended DAPT significantly reduced the risks of ischemic events compared with aspirin monotherapy in a couple of trials, comparison between P2Y12-inhibitor monotherapy and prolonged DAPT for recurrent ischemic events over a longer period beyond 1 year is of great importance,” they say.
They cite two other trials – HOST-EXAM and GLOBAL LEADERS – which have shown P2Y12-inhibitor monotherapy to be superior to aspirin monotherapy in preventing both ischemic and bleeding events during the long-term maintenance period after PCI.
“Combining the results of the current study, HOST-EXAM trial, and landmark analysis of the GLOBAL LEADERS trial, long-term P2Y12-inhibitor monotherapy after a minimum period of DAPT might be the most reliable option from among aspirin monotherapy, P2Y12 monotherapy, and extended DAPT for maintenance therapy after stabilizing patients who have undergone PCI with a current-generation DES,” they conclude.
They note that the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions guidelines for coronary artery revascularization newly recommends a shorter course of DAPT followed by P2Y12 monotherapy as a class IIa indication. The recommendation is based on results of five large, randomized clinical trials, including SMART-CHOICE, TWILIGHT, STOPDAPT-2, TICO, and GLOBAL LEADERS.
“The current results of extended follow-up from the SMART-CHOICE trial support evidence of aspirin-dropping strategy with indefinite use of P2Y12 inhibitor after minimum use of DAPT in patients who underwent PCI,” they say.
They point out that two further trials, A-CLOSE in high-risk patients and SMART-CHOICE III, will be helpful to confirm these findings.
P2Y12-inhibitor monotherapy ‘attractive concept’
In an accompanying editor’s note, Ajay Kirtane, MD, Columbia University Irving Medical Center/New York–Presbyterian Hospital, New York, and Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai and the Cardiovascular Research Foundation, New York, note that current guidelines recommend 3-6 months of DAPT following PCI with current-generation drug-eluting stents in stable patients and 6-12 months or longer for those with acute coronary syndromes. For patients at higher risk of bleeding, even shorter DAPT durations can be considered on a case-by-case basis.
Historically, the component of DAPT subject to discontinuation decisions was the P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor), but more recent trials have further explored whether discontinuation of the aspirin component of DAPT can mitigate bleeding while preserving anti-ischemic efficacy.
The editorialists explain that the concept of P2Y1-inhibitor monotherapy is attractive because it may optimize antiplatelet effects through a single agent that can avoid the gastrointestinal toxicity of aspirin as well as the increased bleeding that comes with combing multiple antithrombotic agents.
They suggest that the long-term results from the SMART-CHOICE trial “should lead clinicians to consider a strategy of monotherapy after a short period of DAPT as a viable one to mitigate bleeding risk,” although they also point out that SMART-CHOICE was underpowered to rigorously assess ischemic differences, so caution is warranted.
“For patients at greatest risk for recurrent ischemic events, the role of continued DAPT is always an option, but these data (and other consistent trials) give clinicians more options to pursue individualized treatment decisions,” they write.
“To some, the continually moving field of post-PCI antiplatelet therapy has provided too many choices, which can at times be dizzying. To us, every patient is different, and thoughtful evidence-based consideration is increasingly possible for many of our treatment decisions,” they conclude.
The SMART-CHOICE study was supported by unrestricted grants from the Korean Society of Interventional Cardiology, Abbott Vascular, Biotronik, and Boston Scientific.
A version of this article first appeared on Medscape.com.
FROM JAMA CARDIOLOGY
Aspirin primary prevention benefit in those with raised Lp(a)?
Aspirin may be of specific benefit for the primary prevention of cardiovascular disease in individuals with raised Lp(a) levels, a new study has suggested.
The study analyzed data from the ASPREE (ASPirin in Reducing Events in the Elderly) trial, which randomized 19,000 individuals aged 70 years or older without a history of cardiovascular disease to aspirin (100 mg/day) or placebo. While the main results, reported previously, showed no net benefit of aspirin in the overall population, the current analysis suggests there may be a benefit in individuals with raised Lp(a) levels.
The current analysis was published online in the Journal of the American College of Cardiology.
“Our study provides evidence that aspirin may specifically benefit older individuals with genotypes for elevated plasma Lp(a) in the setting of high-risk primary prevention of cardiovascular events and that overall benefit may outweigh harm related to major bleeding,” the authors, led by Paul Lacaze, PhD, Monash University, Melbourne, conclude.
They also point out that similar observations have been previously seen in another large aspirin primary prevention study conducted in younger women, the Women’s Health Study, and the current analysis provides validation of those findings.
“Our results provide new evidence to support the potential use of aspirin to target individuals with elevated Lp(a) for the primary prevention of cardiovascular events,” the researchers say.
They acknowledge that these results would be strengthened by the use of directly measured plasma Lp(a) levels, in addition to Lp(a) genotypes.
But they add: “Nonetheless, given the lack of any currently approved therapies for targeting elevated Lp(a), our findings may have widespread clinical implications, adding evidence to the rationale that aspirin may be a viable option for reducing Lp(a)-mediated cardiovascular risk.”
Dr. Lacaze and colleagues explain that elevated plasma Lp(a) levels confer up to fourfold increased risk of cardiovascular disease, with around 20%-30% of the general population affected. Despite the high burden and prevalence of elevated plasma Lp(a), there are currently no approved pharmacologic therapies targeting this lipoprotein. Although promising candidates are in development for the secondary prevention of Lp(a)-mediated cardiovascular disease, it will be many years before these candidates are assessed for primary prevention.
For the current study, researchers analyzed data from 12,815 ASPREE participants who had undergone genotyping and compared outcomes with aspirin versus placebo in those with and without genotypes associated with elevated Lp(a) levels.
Results showed that individuals with elevated Lp(a)-associated genotypes, defined in two different ways, showed a reduction in ischemic events with aspirin versus placebo, and this benefit was not outweighed by an increased bleeding risk.
Specifically, in the placebo group, individuals who carried the rs3798220-C allele, which is known to be associated with raised Lp(a) levels, making up 3.2% of the genotyped population in the study, had an almost twofold increased risk of major adverse cardiovascular events than those not carrying this genotype. However, the risk was attenuated in the aspirin group, with carriers of the rs3798220-C allele actually having a lower rate of cardiovascular events than noncarriers.
In addition, rs3798220-C carrier status was not significantly associated with increased risk of clinically significant bleeding events in the aspirin group.
Similar results were seen with the second way of identifying patients with a high risk of elevated Lp(a) levels using a 43-variant genetic risk score (LPA-GRS).
In the whole study population, aspirin reduced major adverse cardiovascular events by 1.7 events per 1,000 person-years and increased clinically significant bleeding events by 1.7 events per 1,000 person-years, suggesting parity between overall benefit versus harm.
However, in the rs3798220-C subgroup, aspirin reduced major adverse cardiovascular events by 11.4 events per 1,000 person-years (a more than sixfold higher magnitude of cardiovascular disease risk reduction than in the overall cohort), with a bleeding risk of 3.3 events per 1,000 person-years, the researchers report.
“Hence in rs3798220-C carriers, aspirin appeared to have a net benefit of 8.1 events per 1,000 person-years,” they state.
In the highest LPA-GRS quintile, aspirin reduced major adverse cardiovascular events by 3.3 events per 1,000 person-years (approximately twofold higher magnitude of risk reduction, compared with the overall cohort), with an increase in bleeding risk of 1.6 events per 1,000 person-years (almost identical bleeding risk to the overall cohort). This shifted the benefit versus harm balance in the highest LPA-GRS quintile to a net benefit of 1.7 events per 1,000 person-years.
Similar findings in the Women’s Health Study
Dr. Lacaze and colleagues point out that similar results have also been seen in another large aspirin primary prevention study – the Women’s Health Study (WHS).
The WHS compared aspirin 100 mg every other day with placebo in initially healthy younger women. Previously reported results showed that women carrying the rs3798220-C variant, associated with highly elevated Lp(a) levels, had a twofold higher risk of cardiovascular events than noncarrier women in the placebo group, but this risk was reduced in the aspirin group. And there was no increased risk of bleeding in women with elevated Lp(a).
“These results, in the absence of any other randomized controlled trial evidence or approved therapy for treating Lp(a)-associated risk, have been used by some physicians as justification for prescribing aspirin in patients with elevated Lp(a),” Dr. Lacaze and colleagues note.
“In the present study of the ASPREE trial population, our results were consistent with the WHS analysis, despite randomizing older individuals (both men and women),” they add.
They say this validation of the WHS result provides evidence that a very high-risk subgroup of individuals with highly elevated Lp(a) – those carrying the rs3798220-C allele – may benefit from low-dose aspirin for the primary prevention of cardiovascular events. Further, the benefits in this subgroup specifically may outweigh any bleeding risk.
But they point out that rs3798220-C carriers comprise only a small portion of all individuals with elevated Lp(a) in the general population, while the polygenic LPA-GRS explains about 60% of the variation in directly measured plasma Lp(a) levels and has the potential advantage of being able to identify a larger group of individuals at increased risk.
The researchers note, however, that it is not clear to what extent the LPA-GRS results add further evidence to suggest that individuals with elevated Lp(a), beyond rs3798220-C carriers, may be more likely to benefit from aspirin.
“If the benefit of aspirin extends beyond very high-risk rs3798220-C carriers alone, to the broader 20%-30% of individuals with elevated Lp(a), the potential utility of aspirin for the primary prevention of cardiovascular events would increase substantially,” they say.
‘Very high clinical relevance’
In an accompanying editorial, Ana Devesa, MD, Borja Ibanez, MD, PhD, and Valentin Fuster, MD, PhD, The National Center for Cardiovascular Research, Madrid, say that: “[Dr.] Lacaze et al. are to be congratulated for a study of very high clinical relevance that represents a first indication for primary prevention for patients at high cardiovascular risk.”
They explain that the pathogenic mechanism of Lp(a) is believed to be a combination of prothrombotic and proatherogenic effects, and the current findings support the hypothesis that the prothrombotic mechanism of Lp(a) is mediated by platelet aggregation.
This would explain the occurrence of thrombotic events in the presence of atherosclerosis in that elevated Lp(a) levels may induce platelet adhesion and aggregation to the activated atherosclerotic plaque, thus enhancing the atherothrombotic process. Moreover, activated platelets release several mediators that result in cell adhesion and attraction of chemokines and proinflammatory cytokines, driving an inflammatory response and mediating atherosclerosis progression, they add.
The editorialists highlight the limitations of the study already acknowledged by the authors: The analysis used genotypes rather than elevated Lp(a) levels and included only those of European ancestry, meaning the results are difficult to extrapolate to other populations.
“The next steps in clinical practice should be defined, and there are still questions to be answered,” they conclude. “Will every patient benefit from antithrombotic therapies? Should all patients who have elevated Lp(a) levels be treated with aspirin?”
The ASPREE Biobank is supported by grants from the Commonwealth Scientific and Industrial Research Organisation, Monash University, Menzies Research Institute, Australian National University, University of Melbourne, National Institutes of Health, National Health and Medical Research Council of Australia, and the Victorian Cancer Agency. Dr. Lacaze is supported by a National Heart Foundation Future Leader Fellowship.
A version of this article first appeared on Medscape.com.
Aspirin may be of specific benefit for the primary prevention of cardiovascular disease in individuals with raised Lp(a) levels, a new study has suggested.
The study analyzed data from the ASPREE (ASPirin in Reducing Events in the Elderly) trial, which randomized 19,000 individuals aged 70 years or older without a history of cardiovascular disease to aspirin (100 mg/day) or placebo. While the main results, reported previously, showed no net benefit of aspirin in the overall population, the current analysis suggests there may be a benefit in individuals with raised Lp(a) levels.
The current analysis was published online in the Journal of the American College of Cardiology.
“Our study provides evidence that aspirin may specifically benefit older individuals with genotypes for elevated plasma Lp(a) in the setting of high-risk primary prevention of cardiovascular events and that overall benefit may outweigh harm related to major bleeding,” the authors, led by Paul Lacaze, PhD, Monash University, Melbourne, conclude.
They also point out that similar observations have been previously seen in another large aspirin primary prevention study conducted in younger women, the Women’s Health Study, and the current analysis provides validation of those findings.
“Our results provide new evidence to support the potential use of aspirin to target individuals with elevated Lp(a) for the primary prevention of cardiovascular events,” the researchers say.
They acknowledge that these results would be strengthened by the use of directly measured plasma Lp(a) levels, in addition to Lp(a) genotypes.
But they add: “Nonetheless, given the lack of any currently approved therapies for targeting elevated Lp(a), our findings may have widespread clinical implications, adding evidence to the rationale that aspirin may be a viable option for reducing Lp(a)-mediated cardiovascular risk.”
Dr. Lacaze and colleagues explain that elevated plasma Lp(a) levels confer up to fourfold increased risk of cardiovascular disease, with around 20%-30% of the general population affected. Despite the high burden and prevalence of elevated plasma Lp(a), there are currently no approved pharmacologic therapies targeting this lipoprotein. Although promising candidates are in development for the secondary prevention of Lp(a)-mediated cardiovascular disease, it will be many years before these candidates are assessed for primary prevention.
For the current study, researchers analyzed data from 12,815 ASPREE participants who had undergone genotyping and compared outcomes with aspirin versus placebo in those with and without genotypes associated with elevated Lp(a) levels.
Results showed that individuals with elevated Lp(a)-associated genotypes, defined in two different ways, showed a reduction in ischemic events with aspirin versus placebo, and this benefit was not outweighed by an increased bleeding risk.
Specifically, in the placebo group, individuals who carried the rs3798220-C allele, which is known to be associated with raised Lp(a) levels, making up 3.2% of the genotyped population in the study, had an almost twofold increased risk of major adverse cardiovascular events than those not carrying this genotype. However, the risk was attenuated in the aspirin group, with carriers of the rs3798220-C allele actually having a lower rate of cardiovascular events than noncarriers.
In addition, rs3798220-C carrier status was not significantly associated with increased risk of clinically significant bleeding events in the aspirin group.
Similar results were seen with the second way of identifying patients with a high risk of elevated Lp(a) levels using a 43-variant genetic risk score (LPA-GRS).
In the whole study population, aspirin reduced major adverse cardiovascular events by 1.7 events per 1,000 person-years and increased clinically significant bleeding events by 1.7 events per 1,000 person-years, suggesting parity between overall benefit versus harm.
However, in the rs3798220-C subgroup, aspirin reduced major adverse cardiovascular events by 11.4 events per 1,000 person-years (a more than sixfold higher magnitude of cardiovascular disease risk reduction than in the overall cohort), with a bleeding risk of 3.3 events per 1,000 person-years, the researchers report.
“Hence in rs3798220-C carriers, aspirin appeared to have a net benefit of 8.1 events per 1,000 person-years,” they state.
In the highest LPA-GRS quintile, aspirin reduced major adverse cardiovascular events by 3.3 events per 1,000 person-years (approximately twofold higher magnitude of risk reduction, compared with the overall cohort), with an increase in bleeding risk of 1.6 events per 1,000 person-years (almost identical bleeding risk to the overall cohort). This shifted the benefit versus harm balance in the highest LPA-GRS quintile to a net benefit of 1.7 events per 1,000 person-years.
Similar findings in the Women’s Health Study
Dr. Lacaze and colleagues point out that similar results have also been seen in another large aspirin primary prevention study – the Women’s Health Study (WHS).
The WHS compared aspirin 100 mg every other day with placebo in initially healthy younger women. Previously reported results showed that women carrying the rs3798220-C variant, associated with highly elevated Lp(a) levels, had a twofold higher risk of cardiovascular events than noncarrier women in the placebo group, but this risk was reduced in the aspirin group. And there was no increased risk of bleeding in women with elevated Lp(a).
“These results, in the absence of any other randomized controlled trial evidence or approved therapy for treating Lp(a)-associated risk, have been used by some physicians as justification for prescribing aspirin in patients with elevated Lp(a),” Dr. Lacaze and colleagues note.
“In the present study of the ASPREE trial population, our results were consistent with the WHS analysis, despite randomizing older individuals (both men and women),” they add.
They say this validation of the WHS result provides evidence that a very high-risk subgroup of individuals with highly elevated Lp(a) – those carrying the rs3798220-C allele – may benefit from low-dose aspirin for the primary prevention of cardiovascular events. Further, the benefits in this subgroup specifically may outweigh any bleeding risk.
But they point out that rs3798220-C carriers comprise only a small portion of all individuals with elevated Lp(a) in the general population, while the polygenic LPA-GRS explains about 60% of the variation in directly measured plasma Lp(a) levels and has the potential advantage of being able to identify a larger group of individuals at increased risk.
The researchers note, however, that it is not clear to what extent the LPA-GRS results add further evidence to suggest that individuals with elevated Lp(a), beyond rs3798220-C carriers, may be more likely to benefit from aspirin.
“If the benefit of aspirin extends beyond very high-risk rs3798220-C carriers alone, to the broader 20%-30% of individuals with elevated Lp(a), the potential utility of aspirin for the primary prevention of cardiovascular events would increase substantially,” they say.
‘Very high clinical relevance’
In an accompanying editorial, Ana Devesa, MD, Borja Ibanez, MD, PhD, and Valentin Fuster, MD, PhD, The National Center for Cardiovascular Research, Madrid, say that: “[Dr.] Lacaze et al. are to be congratulated for a study of very high clinical relevance that represents a first indication for primary prevention for patients at high cardiovascular risk.”
They explain that the pathogenic mechanism of Lp(a) is believed to be a combination of prothrombotic and proatherogenic effects, and the current findings support the hypothesis that the prothrombotic mechanism of Lp(a) is mediated by platelet aggregation.
This would explain the occurrence of thrombotic events in the presence of atherosclerosis in that elevated Lp(a) levels may induce platelet adhesion and aggregation to the activated atherosclerotic plaque, thus enhancing the atherothrombotic process. Moreover, activated platelets release several mediators that result in cell adhesion and attraction of chemokines and proinflammatory cytokines, driving an inflammatory response and mediating atherosclerosis progression, they add.
The editorialists highlight the limitations of the study already acknowledged by the authors: The analysis used genotypes rather than elevated Lp(a) levels and included only those of European ancestry, meaning the results are difficult to extrapolate to other populations.
“The next steps in clinical practice should be defined, and there are still questions to be answered,” they conclude. “Will every patient benefit from antithrombotic therapies? Should all patients who have elevated Lp(a) levels be treated with aspirin?”
The ASPREE Biobank is supported by grants from the Commonwealth Scientific and Industrial Research Organisation, Monash University, Menzies Research Institute, Australian National University, University of Melbourne, National Institutes of Health, National Health and Medical Research Council of Australia, and the Victorian Cancer Agency. Dr. Lacaze is supported by a National Heart Foundation Future Leader Fellowship.
A version of this article first appeared on Medscape.com.
Aspirin may be of specific benefit for the primary prevention of cardiovascular disease in individuals with raised Lp(a) levels, a new study has suggested.
The study analyzed data from the ASPREE (ASPirin in Reducing Events in the Elderly) trial, which randomized 19,000 individuals aged 70 years or older without a history of cardiovascular disease to aspirin (100 mg/day) or placebo. While the main results, reported previously, showed no net benefit of aspirin in the overall population, the current analysis suggests there may be a benefit in individuals with raised Lp(a) levels.
The current analysis was published online in the Journal of the American College of Cardiology.
“Our study provides evidence that aspirin may specifically benefit older individuals with genotypes for elevated plasma Lp(a) in the setting of high-risk primary prevention of cardiovascular events and that overall benefit may outweigh harm related to major bleeding,” the authors, led by Paul Lacaze, PhD, Monash University, Melbourne, conclude.
They also point out that similar observations have been previously seen in another large aspirin primary prevention study conducted in younger women, the Women’s Health Study, and the current analysis provides validation of those findings.
“Our results provide new evidence to support the potential use of aspirin to target individuals with elevated Lp(a) for the primary prevention of cardiovascular events,” the researchers say.
They acknowledge that these results would be strengthened by the use of directly measured plasma Lp(a) levels, in addition to Lp(a) genotypes.
But they add: “Nonetheless, given the lack of any currently approved therapies for targeting elevated Lp(a), our findings may have widespread clinical implications, adding evidence to the rationale that aspirin may be a viable option for reducing Lp(a)-mediated cardiovascular risk.”
Dr. Lacaze and colleagues explain that elevated plasma Lp(a) levels confer up to fourfold increased risk of cardiovascular disease, with around 20%-30% of the general population affected. Despite the high burden and prevalence of elevated plasma Lp(a), there are currently no approved pharmacologic therapies targeting this lipoprotein. Although promising candidates are in development for the secondary prevention of Lp(a)-mediated cardiovascular disease, it will be many years before these candidates are assessed for primary prevention.
For the current study, researchers analyzed data from 12,815 ASPREE participants who had undergone genotyping and compared outcomes with aspirin versus placebo in those with and without genotypes associated with elevated Lp(a) levels.
Results showed that individuals with elevated Lp(a)-associated genotypes, defined in two different ways, showed a reduction in ischemic events with aspirin versus placebo, and this benefit was not outweighed by an increased bleeding risk.
Specifically, in the placebo group, individuals who carried the rs3798220-C allele, which is known to be associated with raised Lp(a) levels, making up 3.2% of the genotyped population in the study, had an almost twofold increased risk of major adverse cardiovascular events than those not carrying this genotype. However, the risk was attenuated in the aspirin group, with carriers of the rs3798220-C allele actually having a lower rate of cardiovascular events than noncarriers.
In addition, rs3798220-C carrier status was not significantly associated with increased risk of clinically significant bleeding events in the aspirin group.
Similar results were seen with the second way of identifying patients with a high risk of elevated Lp(a) levels using a 43-variant genetic risk score (LPA-GRS).
In the whole study population, aspirin reduced major adverse cardiovascular events by 1.7 events per 1,000 person-years and increased clinically significant bleeding events by 1.7 events per 1,000 person-years, suggesting parity between overall benefit versus harm.
However, in the rs3798220-C subgroup, aspirin reduced major adverse cardiovascular events by 11.4 events per 1,000 person-years (a more than sixfold higher magnitude of cardiovascular disease risk reduction than in the overall cohort), with a bleeding risk of 3.3 events per 1,000 person-years, the researchers report.
“Hence in rs3798220-C carriers, aspirin appeared to have a net benefit of 8.1 events per 1,000 person-years,” they state.
In the highest LPA-GRS quintile, aspirin reduced major adverse cardiovascular events by 3.3 events per 1,000 person-years (approximately twofold higher magnitude of risk reduction, compared with the overall cohort), with an increase in bleeding risk of 1.6 events per 1,000 person-years (almost identical bleeding risk to the overall cohort). This shifted the benefit versus harm balance in the highest LPA-GRS quintile to a net benefit of 1.7 events per 1,000 person-years.
Similar findings in the Women’s Health Study
Dr. Lacaze and colleagues point out that similar results have also been seen in another large aspirin primary prevention study – the Women’s Health Study (WHS).
The WHS compared aspirin 100 mg every other day with placebo in initially healthy younger women. Previously reported results showed that women carrying the rs3798220-C variant, associated with highly elevated Lp(a) levels, had a twofold higher risk of cardiovascular events than noncarrier women in the placebo group, but this risk was reduced in the aspirin group. And there was no increased risk of bleeding in women with elevated Lp(a).
“These results, in the absence of any other randomized controlled trial evidence or approved therapy for treating Lp(a)-associated risk, have been used by some physicians as justification for prescribing aspirin in patients with elevated Lp(a),” Dr. Lacaze and colleagues note.
“In the present study of the ASPREE trial population, our results were consistent with the WHS analysis, despite randomizing older individuals (both men and women),” they add.
They say this validation of the WHS result provides evidence that a very high-risk subgroup of individuals with highly elevated Lp(a) – those carrying the rs3798220-C allele – may benefit from low-dose aspirin for the primary prevention of cardiovascular events. Further, the benefits in this subgroup specifically may outweigh any bleeding risk.
But they point out that rs3798220-C carriers comprise only a small portion of all individuals with elevated Lp(a) in the general population, while the polygenic LPA-GRS explains about 60% of the variation in directly measured plasma Lp(a) levels and has the potential advantage of being able to identify a larger group of individuals at increased risk.
The researchers note, however, that it is not clear to what extent the LPA-GRS results add further evidence to suggest that individuals with elevated Lp(a), beyond rs3798220-C carriers, may be more likely to benefit from aspirin.
“If the benefit of aspirin extends beyond very high-risk rs3798220-C carriers alone, to the broader 20%-30% of individuals with elevated Lp(a), the potential utility of aspirin for the primary prevention of cardiovascular events would increase substantially,” they say.
‘Very high clinical relevance’
In an accompanying editorial, Ana Devesa, MD, Borja Ibanez, MD, PhD, and Valentin Fuster, MD, PhD, The National Center for Cardiovascular Research, Madrid, say that: “[Dr.] Lacaze et al. are to be congratulated for a study of very high clinical relevance that represents a first indication for primary prevention for patients at high cardiovascular risk.”
They explain that the pathogenic mechanism of Lp(a) is believed to be a combination of prothrombotic and proatherogenic effects, and the current findings support the hypothesis that the prothrombotic mechanism of Lp(a) is mediated by platelet aggregation.
This would explain the occurrence of thrombotic events in the presence of atherosclerosis in that elevated Lp(a) levels may induce platelet adhesion and aggregation to the activated atherosclerotic plaque, thus enhancing the atherothrombotic process. Moreover, activated platelets release several mediators that result in cell adhesion and attraction of chemokines and proinflammatory cytokines, driving an inflammatory response and mediating atherosclerosis progression, they add.
The editorialists highlight the limitations of the study already acknowledged by the authors: The analysis used genotypes rather than elevated Lp(a) levels and included only those of European ancestry, meaning the results are difficult to extrapolate to other populations.
“The next steps in clinical practice should be defined, and there are still questions to be answered,” they conclude. “Will every patient benefit from antithrombotic therapies? Should all patients who have elevated Lp(a) levels be treated with aspirin?”
The ASPREE Biobank is supported by grants from the Commonwealth Scientific and Industrial Research Organisation, Monash University, Menzies Research Institute, Australian National University, University of Melbourne, National Institutes of Health, National Health and Medical Research Council of Australia, and the Victorian Cancer Agency. Dr. Lacaze is supported by a National Heart Foundation Future Leader Fellowship.
A version of this article first appeared on Medscape.com.
Coffee linked to reduced cardiovascular disease and mortality risk
Drinking two to three daily cups of – ground, instant, or decaffeinated – is associated with significant reductions in new cardiovascular disease (CVD) and mortality risk, compared with avoiding coffee, a new analysis of the prospective UK Biobank suggests.
Ground and instant coffee, but not decaffeinated coffee, also was associated with reduced risk of new-onset arrhythmia, including atrial fibrillation.
“Our study is the first to look at differences in coffee subtypes to tease out important differences which may explain some of the mechanisms through which coffee works,” Peter M. Kistler, MD, of the Alfred Hospital and Baker Heart and Diabetes Institute, Melbourne, Australia, told this news organization.
“Daily coffee intake should not be discouraged by physicians but rather considered part of a healthy diet,” Dr. Kistler said.
“This study supports that coffee is safe and even potentially beneficial, which is consistent with most of the prior evidence,” Carl “Chip” Lavie, MD, who wasn’t involved in the study, told this news organization.
“We do not prescribe coffee to patients, but for the majority who like coffee, they can be encouraged it is fine to take a few cups daily,” said Dr. Lavie, with the Ochsner Heart and Vascular Institute in New Orleans.
The study was published online in the European Journal of Preventive Cardiology.
Clear cardiovascular benefits
A total of 449,563 UK Biobank participants (median age 58 years; 55% women), who were free of arrhythmias or other CVD at baseline, reported in questionnaires their level of daily coffee intake and preferred type of coffee.
During more than 12.5 years of follow-up, 27,809 participants (6.2%) died.
Drinking one to five cups per day of ground or instant coffee (but not decaffeinated coffee) was associated with a significant reduction in incident arrhythmia. The lowest risk was with four to five cups per day for ground coffee (hazard ratio [HR] 0.83; 95% confidence interval [CI], 0.76-0.91; P < .0001) and two to three cups per day for instant coffee (HR, 0.88; 95% CI, 0.85-0.92; P < .0001).
Habitual coffee drinking of up to five cups perday was also associated with significant reductions in the risk of incident CVD, when compared with nondrinkers.
Significant reductions in the risk of incident coronary heart disease (CHD) were associated with habitual coffee intake of up to five cups per day, with the lowest risk for CHD observed in those who consumed two to three cups per day (HR 0.89; 95% CI, 0.86-0.91; P < .0001).
Coffee consumption at all levels was linked to significant reduction in the risk of congestive cardiac failure (CCF) and ischemic stroke. The lowest risks were observed in those who consumed two to three cups per day, with HR, 0.83 (95% CI, 0.79-0.87; P < .0001) for CCF and HR, 0.84 (95% CI, 0.78-0.90; P < .0001) for ischemic stroke.
Death from any cause was significantly reduced for all coffee subtypes, with the greatest risk reduction seen with two to three cups per day for decaffeinated (HR, 0.86; 95% CI, 0.81-0.91; P < .0001); ground (HR, 0.73; 95% CI, 0.69-0.78; P < .0001); and instant coffee (HR, 0.89; 95% CI, 0.86-0.93; P < .0001).
“Coffee consumption is associated with cardiovascular benefits and should not empirically be discontinued in those with underlying heart rhythm disorders or cardiovascular disease,” Dr. Kistler told this news organization.
Plausible mechanisms
There are a number of proposed mechanisms to explain the benefits of coffee on CVD.
“Caffeine has antiarrhythmic properties through adenosine A1 and A2A receptor inhibition, hence the difference in effects of decaf vs. full-strength coffee on heart rhythm disorders,” Dr. Kistler explained.
Coffee has vasodilatory effects and coffee also contains antioxidant polyphenols, which reduce oxidative stress and modulate metabolism.
“The explanation for improved survival with habitual coffee consumption remains unclear,” Dr. Kistler said.
“Putative mechanisms include improved endothelial function, circulating antioxidants, improved insulin sensitivity, and reduced inflammation. Another potential mechanism includes the beneficial effects of coffee on metabolic syndrome,” he said.
“Caffeine has a role in weight loss through inhibition of gut fatty acid absorption and increase in basal metabolic rate. Furthermore, coffee has been associated with a significantly lower incidence of type 2 diabetes mellitus,” Dr. Kistler added.
Direction of relationship unclear
Charlotte Mills, PhD, University of Reading, England, said this study “adds to the body of evidence from observational trials associating moderate coffee consumption with cardioprotection, which looks promising.”
However, with the observational design, it’s unclear “which direction the relationship goes – for example, does coffee make you healthy or do inherently healthier people consume coffee? Randomized controlled trials are needed to fully understand the relationship between coffee and health before recommendations can be made,” Dr. Mills told the UK nonprofit Science Media Centre.
Annette Creedon, PhD, nutrition scientist with the British Nutrition Foundation, said it’s possible that respondents over- or underestimated the amount of coffee that they were consuming at the start of the study when they self-reported their intake.
“It is therefore difficult to determine whether the outcomes can be directly associated with the behaviors in coffee consumption reported at the start of the study,” she told the Science Media Centre.
The study had no funding. Dr. Kistler has received funding from Abbott Medical for consultancy and speaking engagements and fellowship support from Biosense Webster. Dr. Lavie has no relevant disclosures. Dr. Mills has worked in collaboration with Nestle on research relating to coffee and health funded by UKRI. Dr. Creedon has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Drinking two to three daily cups of – ground, instant, or decaffeinated – is associated with significant reductions in new cardiovascular disease (CVD) and mortality risk, compared with avoiding coffee, a new analysis of the prospective UK Biobank suggests.
Ground and instant coffee, but not decaffeinated coffee, also was associated with reduced risk of new-onset arrhythmia, including atrial fibrillation.
“Our study is the first to look at differences in coffee subtypes to tease out important differences which may explain some of the mechanisms through which coffee works,” Peter M. Kistler, MD, of the Alfred Hospital and Baker Heart and Diabetes Institute, Melbourne, Australia, told this news organization.
“Daily coffee intake should not be discouraged by physicians but rather considered part of a healthy diet,” Dr. Kistler said.
“This study supports that coffee is safe and even potentially beneficial, which is consistent with most of the prior evidence,” Carl “Chip” Lavie, MD, who wasn’t involved in the study, told this news organization.
“We do not prescribe coffee to patients, but for the majority who like coffee, they can be encouraged it is fine to take a few cups daily,” said Dr. Lavie, with the Ochsner Heart and Vascular Institute in New Orleans.
The study was published online in the European Journal of Preventive Cardiology.
Clear cardiovascular benefits
A total of 449,563 UK Biobank participants (median age 58 years; 55% women), who were free of arrhythmias or other CVD at baseline, reported in questionnaires their level of daily coffee intake and preferred type of coffee.
During more than 12.5 years of follow-up, 27,809 participants (6.2%) died.
Drinking one to five cups per day of ground or instant coffee (but not decaffeinated coffee) was associated with a significant reduction in incident arrhythmia. The lowest risk was with four to five cups per day for ground coffee (hazard ratio [HR] 0.83; 95% confidence interval [CI], 0.76-0.91; P < .0001) and two to three cups per day for instant coffee (HR, 0.88; 95% CI, 0.85-0.92; P < .0001).
Habitual coffee drinking of up to five cups perday was also associated with significant reductions in the risk of incident CVD, when compared with nondrinkers.
Significant reductions in the risk of incident coronary heart disease (CHD) were associated with habitual coffee intake of up to five cups per day, with the lowest risk for CHD observed in those who consumed two to three cups per day (HR 0.89; 95% CI, 0.86-0.91; P < .0001).
Coffee consumption at all levels was linked to significant reduction in the risk of congestive cardiac failure (CCF) and ischemic stroke. The lowest risks were observed in those who consumed two to three cups per day, with HR, 0.83 (95% CI, 0.79-0.87; P < .0001) for CCF and HR, 0.84 (95% CI, 0.78-0.90; P < .0001) for ischemic stroke.
Death from any cause was significantly reduced for all coffee subtypes, with the greatest risk reduction seen with two to three cups per day for decaffeinated (HR, 0.86; 95% CI, 0.81-0.91; P < .0001); ground (HR, 0.73; 95% CI, 0.69-0.78; P < .0001); and instant coffee (HR, 0.89; 95% CI, 0.86-0.93; P < .0001).
“Coffee consumption is associated with cardiovascular benefits and should not empirically be discontinued in those with underlying heart rhythm disorders or cardiovascular disease,” Dr. Kistler told this news organization.
Plausible mechanisms
There are a number of proposed mechanisms to explain the benefits of coffee on CVD.
“Caffeine has antiarrhythmic properties through adenosine A1 and A2A receptor inhibition, hence the difference in effects of decaf vs. full-strength coffee on heart rhythm disorders,” Dr. Kistler explained.
Coffee has vasodilatory effects and coffee also contains antioxidant polyphenols, which reduce oxidative stress and modulate metabolism.
“The explanation for improved survival with habitual coffee consumption remains unclear,” Dr. Kistler said.
“Putative mechanisms include improved endothelial function, circulating antioxidants, improved insulin sensitivity, and reduced inflammation. Another potential mechanism includes the beneficial effects of coffee on metabolic syndrome,” he said.
“Caffeine has a role in weight loss through inhibition of gut fatty acid absorption and increase in basal metabolic rate. Furthermore, coffee has been associated with a significantly lower incidence of type 2 diabetes mellitus,” Dr. Kistler added.
Direction of relationship unclear
Charlotte Mills, PhD, University of Reading, England, said this study “adds to the body of evidence from observational trials associating moderate coffee consumption with cardioprotection, which looks promising.”
However, with the observational design, it’s unclear “which direction the relationship goes – for example, does coffee make you healthy or do inherently healthier people consume coffee? Randomized controlled trials are needed to fully understand the relationship between coffee and health before recommendations can be made,” Dr. Mills told the UK nonprofit Science Media Centre.
Annette Creedon, PhD, nutrition scientist with the British Nutrition Foundation, said it’s possible that respondents over- or underestimated the amount of coffee that they were consuming at the start of the study when they self-reported their intake.
“It is therefore difficult to determine whether the outcomes can be directly associated with the behaviors in coffee consumption reported at the start of the study,” she told the Science Media Centre.
The study had no funding. Dr. Kistler has received funding from Abbott Medical for consultancy and speaking engagements and fellowship support from Biosense Webster. Dr. Lavie has no relevant disclosures. Dr. Mills has worked in collaboration with Nestle on research relating to coffee and health funded by UKRI. Dr. Creedon has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Drinking two to three daily cups of – ground, instant, or decaffeinated – is associated with significant reductions in new cardiovascular disease (CVD) and mortality risk, compared with avoiding coffee, a new analysis of the prospective UK Biobank suggests.
Ground and instant coffee, but not decaffeinated coffee, also was associated with reduced risk of new-onset arrhythmia, including atrial fibrillation.
“Our study is the first to look at differences in coffee subtypes to tease out important differences which may explain some of the mechanisms through which coffee works,” Peter M. Kistler, MD, of the Alfred Hospital and Baker Heart and Diabetes Institute, Melbourne, Australia, told this news organization.
“Daily coffee intake should not be discouraged by physicians but rather considered part of a healthy diet,” Dr. Kistler said.
“This study supports that coffee is safe and even potentially beneficial, which is consistent with most of the prior evidence,” Carl “Chip” Lavie, MD, who wasn’t involved in the study, told this news organization.
“We do not prescribe coffee to patients, but for the majority who like coffee, they can be encouraged it is fine to take a few cups daily,” said Dr. Lavie, with the Ochsner Heart and Vascular Institute in New Orleans.
The study was published online in the European Journal of Preventive Cardiology.
Clear cardiovascular benefits
A total of 449,563 UK Biobank participants (median age 58 years; 55% women), who were free of arrhythmias or other CVD at baseline, reported in questionnaires their level of daily coffee intake and preferred type of coffee.
During more than 12.5 years of follow-up, 27,809 participants (6.2%) died.
Drinking one to five cups per day of ground or instant coffee (but not decaffeinated coffee) was associated with a significant reduction in incident arrhythmia. The lowest risk was with four to five cups per day for ground coffee (hazard ratio [HR] 0.83; 95% confidence interval [CI], 0.76-0.91; P < .0001) and two to three cups per day for instant coffee (HR, 0.88; 95% CI, 0.85-0.92; P < .0001).
Habitual coffee drinking of up to five cups perday was also associated with significant reductions in the risk of incident CVD, when compared with nondrinkers.
Significant reductions in the risk of incident coronary heart disease (CHD) were associated with habitual coffee intake of up to five cups per day, with the lowest risk for CHD observed in those who consumed two to three cups per day (HR 0.89; 95% CI, 0.86-0.91; P < .0001).
Coffee consumption at all levels was linked to significant reduction in the risk of congestive cardiac failure (CCF) and ischemic stroke. The lowest risks were observed in those who consumed two to three cups per day, with HR, 0.83 (95% CI, 0.79-0.87; P < .0001) for CCF and HR, 0.84 (95% CI, 0.78-0.90; P < .0001) for ischemic stroke.
Death from any cause was significantly reduced for all coffee subtypes, with the greatest risk reduction seen with two to three cups per day for decaffeinated (HR, 0.86; 95% CI, 0.81-0.91; P < .0001); ground (HR, 0.73; 95% CI, 0.69-0.78; P < .0001); and instant coffee (HR, 0.89; 95% CI, 0.86-0.93; P < .0001).
“Coffee consumption is associated with cardiovascular benefits and should not empirically be discontinued in those with underlying heart rhythm disorders or cardiovascular disease,” Dr. Kistler told this news organization.
Plausible mechanisms
There are a number of proposed mechanisms to explain the benefits of coffee on CVD.
“Caffeine has antiarrhythmic properties through adenosine A1 and A2A receptor inhibition, hence the difference in effects of decaf vs. full-strength coffee on heart rhythm disorders,” Dr. Kistler explained.
Coffee has vasodilatory effects and coffee also contains antioxidant polyphenols, which reduce oxidative stress and modulate metabolism.
“The explanation for improved survival with habitual coffee consumption remains unclear,” Dr. Kistler said.
“Putative mechanisms include improved endothelial function, circulating antioxidants, improved insulin sensitivity, and reduced inflammation. Another potential mechanism includes the beneficial effects of coffee on metabolic syndrome,” he said.
“Caffeine has a role in weight loss through inhibition of gut fatty acid absorption and increase in basal metabolic rate. Furthermore, coffee has been associated with a significantly lower incidence of type 2 diabetes mellitus,” Dr. Kistler added.
Direction of relationship unclear
Charlotte Mills, PhD, University of Reading, England, said this study “adds to the body of evidence from observational trials associating moderate coffee consumption with cardioprotection, which looks promising.”
However, with the observational design, it’s unclear “which direction the relationship goes – for example, does coffee make you healthy or do inherently healthier people consume coffee? Randomized controlled trials are needed to fully understand the relationship between coffee and health before recommendations can be made,” Dr. Mills told the UK nonprofit Science Media Centre.
Annette Creedon, PhD, nutrition scientist with the British Nutrition Foundation, said it’s possible that respondents over- or underestimated the amount of coffee that they were consuming at the start of the study when they self-reported their intake.
“It is therefore difficult to determine whether the outcomes can be directly associated with the behaviors in coffee consumption reported at the start of the study,” she told the Science Media Centre.
The study had no funding. Dr. Kistler has received funding from Abbott Medical for consultancy and speaking engagements and fellowship support from Biosense Webster. Dr. Lavie has no relevant disclosures. Dr. Mills has worked in collaboration with Nestle on research relating to coffee and health funded by UKRI. Dr. Creedon has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY
Cre8 EVO stent loses sweet spot in diabetes at 2 years: SUGAR
BOSTON – Despite a promising start, extended follow-up from the SUGAR trial found that the Cre8 EVO drug-eluting stent could not maintain superiority over the Resolute Onyx DES at 2 years in patients with diabetes undergoing revascularization for coronary artery disease.
The Cre8 EVO stent (Alvimedica) is not available in the United States but, as previously reported, caused a stir last year after demonstrating a 35% relative risk reduction in the primary endpoint of target lesion failure (TLF) at 1 year in a prespecified superiority analysis.
At 2 years, however, the TLF rate was 10.4% with the polymer-free Cre8 EVO amphilimus-eluting stent and 12.1% with the durable polymer Resolute Onyx (Medtronic) zotarolimus-eluting stent, which did not achieve superiority (hazard ratio, 0.84; 95% confidence interval, 0.60-1.19).
Rates were numerically lower with the Cre8 EVO stent for the endpoint’s individual components of cardiac death (3.1% vs. 3.4%), target vessel MI (6.6% vs. 7.6%), and target lesion revascularization (4.3% vs. 4.6%).
Results were also similar between the Cre8 EVO and Resolute Onyx stents for all-cause mortality (7.1% vs. 6.8%), any MI (9.0% vs. 9.2%), target vessel revascularization (5.5% vs. 5.1%), all new revascularizations (7.6% vs. 9.4%), definite stent thrombosis (1.0% vs. 1.2%), and major adverse cardiac events (18.3% vs. 20.8%), Pablo Salinas, MD, PhD, of Hospital Clinico San Carlos, Madrid, reported at the Transcatheter Cardiovascular Therapeutics annual meeting.
He noted that all-cause mortality was 7% in just 2 years in the diabetic cohort, or twice the number of cardiac deaths. “In other words, these patients had the same chance of dying from cardiac causes and noncardiac causes, so we need a more comprehensive approach to the disease. Also, if you look at all new revascularizations, roughly 50% were off target, so there is disease progression at 2 years in this population.”
Among the 586 Cre8 EVO and 589 Resolute Onyx patients who underwent percutaneous coronary intervention (PCI), roughly half had multivessel coronary artery disease, 83% had hypertension, 81% had dyslipidemia, and 21% were current smokers. Nearly all patients had diabetes type 2 for an average of 10.6 years for Cre8 EVO and 11.4 years for Resolute Onyx, with hemoglobin A1c levels of 7.4% and 7.5%, respectively.
Although there is “insufficient evidence” the Cre8 EVO stent is superior to the Resolute Onyx stent with regard to TLF, Dr. Salinas concluded extended follow-up until 5 years is warranted.
During a discussion of the results, Dr. Salinas said he expects the 5-year results will “probably go parallel” but that it’s worth following this very valuable cohort. “There are not so many trials with 1,000 diabetic patients. We always speak about how complex they are, the results are bad, but we don’t use the diabetic population in trials,” he said at the meeting sponsored by the Cardiovascular Research Foundation.
Asked during a TCT press conference what could have caused the catch-up in TLF at 2 years, Dr. Salinas said there were only 25 primary events from years 1 to 2, driven primarily by periprocedural MI, but that the timing of restenosis was different. Events accrued “drop by drop” with the Cre8 EVO, whereas with the Resolute Onyx there was a “bump in restenosis” after 6 months “but then it is very nice to see it is flat, which means that durable polymers are also safe because we have not seen late events.”
Press conference discussant Carlo Di Mario, MD, from Careggi University Hospital, Florence, Italy, who was not involved in the study, said the reversal of superiority for the Cre8 EVO might be a “bitter note” for the investigators but “maybe it is not bitter for us because overall, the percentage of figures are so low that it’s very difficult to find a difference” between the two stents.
Roxana Mehran, MD, of Icahn School of Medicine at Mount Sinai, New York, who previously described the 1-year results as “almost too good to be true,” commented to this news organization, “We just saw in this trial, no benefit whatsoever at 2 years in terms of target lesion failure. So it’s very important for us to evaluate this going forward.”
She continued, “We’ve always been talking about these biodegradable polymers and then going back to the bare metal stent – oh that’s great because polymers aren’t so good – but now we’re seeing durable polymers may be okay, especially with the current technology.”
Asked whether Cre8 EVO, which is CE mark certified in Europe, remains an option in light of the new results, Dr. Mehran said, “I don’t think it kills it. It’s not worse; it’s another stent that’s available.”
Nevertheless, “what we’re looking for is some efficacious benefit for diabetic patients. We don’t have one yet,” observed Dr. Mehran, who is leading the ABILITY Diabetes Global trial, which just finished enrolling 3,000 patients with diabetes and is testing PCI with the Abluminus DES+ sirolimus-eluting stent system vs. the Xience everolimus-eluting stent. The study is estimated to be complete in August 2024.
The study was funded by the Spanish Society of Cardiology. Dr. Salinas reported consulting fees/honoraria from Boston Scientific, Abbott Vascular, Biomenco, and Medtronic.
A version of this article first appeared on Medscape.com.
BOSTON – Despite a promising start, extended follow-up from the SUGAR trial found that the Cre8 EVO drug-eluting stent could not maintain superiority over the Resolute Onyx DES at 2 years in patients with diabetes undergoing revascularization for coronary artery disease.
The Cre8 EVO stent (Alvimedica) is not available in the United States but, as previously reported, caused a stir last year after demonstrating a 35% relative risk reduction in the primary endpoint of target lesion failure (TLF) at 1 year in a prespecified superiority analysis.
At 2 years, however, the TLF rate was 10.4% with the polymer-free Cre8 EVO amphilimus-eluting stent and 12.1% with the durable polymer Resolute Onyx (Medtronic) zotarolimus-eluting stent, which did not achieve superiority (hazard ratio, 0.84; 95% confidence interval, 0.60-1.19).
Rates were numerically lower with the Cre8 EVO stent for the endpoint’s individual components of cardiac death (3.1% vs. 3.4%), target vessel MI (6.6% vs. 7.6%), and target lesion revascularization (4.3% vs. 4.6%).
Results were also similar between the Cre8 EVO and Resolute Onyx stents for all-cause mortality (7.1% vs. 6.8%), any MI (9.0% vs. 9.2%), target vessel revascularization (5.5% vs. 5.1%), all new revascularizations (7.6% vs. 9.4%), definite stent thrombosis (1.0% vs. 1.2%), and major adverse cardiac events (18.3% vs. 20.8%), Pablo Salinas, MD, PhD, of Hospital Clinico San Carlos, Madrid, reported at the Transcatheter Cardiovascular Therapeutics annual meeting.
He noted that all-cause mortality was 7% in just 2 years in the diabetic cohort, or twice the number of cardiac deaths. “In other words, these patients had the same chance of dying from cardiac causes and noncardiac causes, so we need a more comprehensive approach to the disease. Also, if you look at all new revascularizations, roughly 50% were off target, so there is disease progression at 2 years in this population.”
Among the 586 Cre8 EVO and 589 Resolute Onyx patients who underwent percutaneous coronary intervention (PCI), roughly half had multivessel coronary artery disease, 83% had hypertension, 81% had dyslipidemia, and 21% were current smokers. Nearly all patients had diabetes type 2 for an average of 10.6 years for Cre8 EVO and 11.4 years for Resolute Onyx, with hemoglobin A1c levels of 7.4% and 7.5%, respectively.
Although there is “insufficient evidence” the Cre8 EVO stent is superior to the Resolute Onyx stent with regard to TLF, Dr. Salinas concluded extended follow-up until 5 years is warranted.
During a discussion of the results, Dr. Salinas said he expects the 5-year results will “probably go parallel” but that it’s worth following this very valuable cohort. “There are not so many trials with 1,000 diabetic patients. We always speak about how complex they are, the results are bad, but we don’t use the diabetic population in trials,” he said at the meeting sponsored by the Cardiovascular Research Foundation.
Asked during a TCT press conference what could have caused the catch-up in TLF at 2 years, Dr. Salinas said there were only 25 primary events from years 1 to 2, driven primarily by periprocedural MI, but that the timing of restenosis was different. Events accrued “drop by drop” with the Cre8 EVO, whereas with the Resolute Onyx there was a “bump in restenosis” after 6 months “but then it is very nice to see it is flat, which means that durable polymers are also safe because we have not seen late events.”
Press conference discussant Carlo Di Mario, MD, from Careggi University Hospital, Florence, Italy, who was not involved in the study, said the reversal of superiority for the Cre8 EVO might be a “bitter note” for the investigators but “maybe it is not bitter for us because overall, the percentage of figures are so low that it’s very difficult to find a difference” between the two stents.
Roxana Mehran, MD, of Icahn School of Medicine at Mount Sinai, New York, who previously described the 1-year results as “almost too good to be true,” commented to this news organization, “We just saw in this trial, no benefit whatsoever at 2 years in terms of target lesion failure. So it’s very important for us to evaluate this going forward.”
She continued, “We’ve always been talking about these biodegradable polymers and then going back to the bare metal stent – oh that’s great because polymers aren’t so good – but now we’re seeing durable polymers may be okay, especially with the current technology.”
Asked whether Cre8 EVO, which is CE mark certified in Europe, remains an option in light of the new results, Dr. Mehran said, “I don’t think it kills it. It’s not worse; it’s another stent that’s available.”
Nevertheless, “what we’re looking for is some efficacious benefit for diabetic patients. We don’t have one yet,” observed Dr. Mehran, who is leading the ABILITY Diabetes Global trial, which just finished enrolling 3,000 patients with diabetes and is testing PCI with the Abluminus DES+ sirolimus-eluting stent system vs. the Xience everolimus-eluting stent. The study is estimated to be complete in August 2024.
The study was funded by the Spanish Society of Cardiology. Dr. Salinas reported consulting fees/honoraria from Boston Scientific, Abbott Vascular, Biomenco, and Medtronic.
A version of this article first appeared on Medscape.com.
BOSTON – Despite a promising start, extended follow-up from the SUGAR trial found that the Cre8 EVO drug-eluting stent could not maintain superiority over the Resolute Onyx DES at 2 years in patients with diabetes undergoing revascularization for coronary artery disease.
The Cre8 EVO stent (Alvimedica) is not available in the United States but, as previously reported, caused a stir last year after demonstrating a 35% relative risk reduction in the primary endpoint of target lesion failure (TLF) at 1 year in a prespecified superiority analysis.
At 2 years, however, the TLF rate was 10.4% with the polymer-free Cre8 EVO amphilimus-eluting stent and 12.1% with the durable polymer Resolute Onyx (Medtronic) zotarolimus-eluting stent, which did not achieve superiority (hazard ratio, 0.84; 95% confidence interval, 0.60-1.19).
Rates were numerically lower with the Cre8 EVO stent for the endpoint’s individual components of cardiac death (3.1% vs. 3.4%), target vessel MI (6.6% vs. 7.6%), and target lesion revascularization (4.3% vs. 4.6%).
Results were also similar between the Cre8 EVO and Resolute Onyx stents for all-cause mortality (7.1% vs. 6.8%), any MI (9.0% vs. 9.2%), target vessel revascularization (5.5% vs. 5.1%), all new revascularizations (7.6% vs. 9.4%), definite stent thrombosis (1.0% vs. 1.2%), and major adverse cardiac events (18.3% vs. 20.8%), Pablo Salinas, MD, PhD, of Hospital Clinico San Carlos, Madrid, reported at the Transcatheter Cardiovascular Therapeutics annual meeting.
He noted that all-cause mortality was 7% in just 2 years in the diabetic cohort, or twice the number of cardiac deaths. “In other words, these patients had the same chance of dying from cardiac causes and noncardiac causes, so we need a more comprehensive approach to the disease. Also, if you look at all new revascularizations, roughly 50% were off target, so there is disease progression at 2 years in this population.”
Among the 586 Cre8 EVO and 589 Resolute Onyx patients who underwent percutaneous coronary intervention (PCI), roughly half had multivessel coronary artery disease, 83% had hypertension, 81% had dyslipidemia, and 21% were current smokers. Nearly all patients had diabetes type 2 for an average of 10.6 years for Cre8 EVO and 11.4 years for Resolute Onyx, with hemoglobin A1c levels of 7.4% and 7.5%, respectively.
Although there is “insufficient evidence” the Cre8 EVO stent is superior to the Resolute Onyx stent with regard to TLF, Dr. Salinas concluded extended follow-up until 5 years is warranted.
During a discussion of the results, Dr. Salinas said he expects the 5-year results will “probably go parallel” but that it’s worth following this very valuable cohort. “There are not so many trials with 1,000 diabetic patients. We always speak about how complex they are, the results are bad, but we don’t use the diabetic population in trials,” he said at the meeting sponsored by the Cardiovascular Research Foundation.
Asked during a TCT press conference what could have caused the catch-up in TLF at 2 years, Dr. Salinas said there were only 25 primary events from years 1 to 2, driven primarily by periprocedural MI, but that the timing of restenosis was different. Events accrued “drop by drop” with the Cre8 EVO, whereas with the Resolute Onyx there was a “bump in restenosis” after 6 months “but then it is very nice to see it is flat, which means that durable polymers are also safe because we have not seen late events.”
Press conference discussant Carlo Di Mario, MD, from Careggi University Hospital, Florence, Italy, who was not involved in the study, said the reversal of superiority for the Cre8 EVO might be a “bitter note” for the investigators but “maybe it is not bitter for us because overall, the percentage of figures are so low that it’s very difficult to find a difference” between the two stents.
Roxana Mehran, MD, of Icahn School of Medicine at Mount Sinai, New York, who previously described the 1-year results as “almost too good to be true,” commented to this news organization, “We just saw in this trial, no benefit whatsoever at 2 years in terms of target lesion failure. So it’s very important for us to evaluate this going forward.”
She continued, “We’ve always been talking about these biodegradable polymers and then going back to the bare metal stent – oh that’s great because polymers aren’t so good – but now we’re seeing durable polymers may be okay, especially with the current technology.”
Asked whether Cre8 EVO, which is CE mark certified in Europe, remains an option in light of the new results, Dr. Mehran said, “I don’t think it kills it. It’s not worse; it’s another stent that’s available.”
Nevertheless, “what we’re looking for is some efficacious benefit for diabetic patients. We don’t have one yet,” observed Dr. Mehran, who is leading the ABILITY Diabetes Global trial, which just finished enrolling 3,000 patients with diabetes and is testing PCI with the Abluminus DES+ sirolimus-eluting stent system vs. the Xience everolimus-eluting stent. The study is estimated to be complete in August 2024.
The study was funded by the Spanish Society of Cardiology. Dr. Salinas reported consulting fees/honoraria from Boston Scientific, Abbott Vascular, Biomenco, and Medtronic.
A version of this article first appeared on Medscape.com.
AT TCT 2022
Uncontrolled BP linked to one-third of ED visits for CVD
A look at the top cardiovascular disease (CVD) diagnoses in U.S. emergency departments (EDs) suggests that many heart-related emergencies are due to poorly controlled high blood pressure.
In a study of more than 20 million ED visits, about one-third of CVD-related ED visits in the United States were for hypertension-related conditions.
Overall, 13% of ED visits, representing more than 2.7 million individuals, were for essential hypertension.
The fact that these visits rarely led to an inpatient admission (< 3%) or death (< 0.1%) suggests they were “mostly related to the management of hypertension,” lead author Mamas A. Mamas, MD, Keele University, Staffordshire, England, said in a news release.
The study was published online in the Journal of the American Heart Association.
Nationwide sample
The researchers studied more than 20.6 million ED encounters in adults with a primary CVD diagnosis using data from the Nationwide Emergency Department Sample between 2016 and 2018.
In the sample, 49% were women, and the median age was 67 years. Men had poorer overall baseline cardiometabolic profiles, but women had higher rates of obesity, hypertension, and cerebrovascular disease. The majority had Medicare or Medicaid insurance.
In women, essential hypertension was the most common reason for an ED visit (16%), followed by hypertensive heart or kidney disease (14%) and atrial fibrillation (AF)/flutter (10%).
In men, the top three reasons were hypertensive heart or kidney disease (15%), essential hypertension (11%), and acute myocardial infarction (AMI, 11%).
On presentation, women were significantly more likely to have essential hypertension, hypertensive crisis, AF/flutter, supraventricular tachycardia, pulmonary embolism, or ischemic stroke, while men were more likely to have AMI, or cardiac arrest.
“Previous studies have shown sex differences in patterns of CVD among hospitalized patients,” Dr. Mamas noted. “However, examining CVD encounters in the ED provides a more complete picture of the cardiovascular healthcare needs of men and women, as it captures encounters prior to hospitalization.”
He noted that previous studies of CVD emergency visits are limited to suspected MI visits. “Therefore, this analysis of 15 CVD conditions helps to better understand the full spectrum of acute CVD needs, including sex disparities in hospitalization and risk of death,” Dr. Mamas said.
Sex differences in outcomes
The study found that outcomes from the emergency CVD visits were slightly different for men and women.
Overall, women were less likely than were men to die (3.3% vs. 4.3%) or be hospitalized (49.1% vs. 52.3%) after an ED visit for CVD. The difference may be due to women’s generally lower-risk diagnoses, Dr. Mamas said, but there could be an underestimation of deaths in women.
In logistic regression models adjusted for baseline covariates, women with intracranial hemorrhage (ICH) had a higher risk of being admitted to hospital or dying compared with men with ICH.
Men were more likely to die if they presented with hypertensive heart or kidney disease, AF/flutter, AMI or cardiac arrest, the researchers found.
“We did not track deaths outside of the hospital setting,” Dr. Mamas pointed out. Given past evidence that women are more likely to be inappropriately discharged from the ED, and strong evidence for the systemic undertreatment of women, further study is warranted to track outcomes beyond the ED visit,” he added.
The researchers called for further research into understanding the underlying factors driving the differences in CVD patterns and outcomes between men and women.
Reached for comment, Maryann McLaughlin, MD, a cardiologist at Mount Sinai Hospital, New York, said: “Hypertension is a silent killer” and this study “reiterates that people need to get their blood pressure checked more regularly.
“In the very least, if they do present to the hospital as not feeling well or whatever it is, and they are identified as having high blood pressure, that’s an important opportunity to really teach them about hypertension and have them follow-up with it,” Dr. McLaughlin told this news organization.
The study was supported by Health Data Research UK. Dr. Keele and Dr. McLaughlin have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A look at the top cardiovascular disease (CVD) diagnoses in U.S. emergency departments (EDs) suggests that many heart-related emergencies are due to poorly controlled high blood pressure.
In a study of more than 20 million ED visits, about one-third of CVD-related ED visits in the United States were for hypertension-related conditions.
Overall, 13% of ED visits, representing more than 2.7 million individuals, were for essential hypertension.
The fact that these visits rarely led to an inpatient admission (< 3%) or death (< 0.1%) suggests they were “mostly related to the management of hypertension,” lead author Mamas A. Mamas, MD, Keele University, Staffordshire, England, said in a news release.
The study was published online in the Journal of the American Heart Association.
Nationwide sample
The researchers studied more than 20.6 million ED encounters in adults with a primary CVD diagnosis using data from the Nationwide Emergency Department Sample between 2016 and 2018.
In the sample, 49% were women, and the median age was 67 years. Men had poorer overall baseline cardiometabolic profiles, but women had higher rates of obesity, hypertension, and cerebrovascular disease. The majority had Medicare or Medicaid insurance.
In women, essential hypertension was the most common reason for an ED visit (16%), followed by hypertensive heart or kidney disease (14%) and atrial fibrillation (AF)/flutter (10%).
In men, the top three reasons were hypertensive heart or kidney disease (15%), essential hypertension (11%), and acute myocardial infarction (AMI, 11%).
On presentation, women were significantly more likely to have essential hypertension, hypertensive crisis, AF/flutter, supraventricular tachycardia, pulmonary embolism, or ischemic stroke, while men were more likely to have AMI, or cardiac arrest.
“Previous studies have shown sex differences in patterns of CVD among hospitalized patients,” Dr. Mamas noted. “However, examining CVD encounters in the ED provides a more complete picture of the cardiovascular healthcare needs of men and women, as it captures encounters prior to hospitalization.”
He noted that previous studies of CVD emergency visits are limited to suspected MI visits. “Therefore, this analysis of 15 CVD conditions helps to better understand the full spectrum of acute CVD needs, including sex disparities in hospitalization and risk of death,” Dr. Mamas said.
Sex differences in outcomes
The study found that outcomes from the emergency CVD visits were slightly different for men and women.
Overall, women were less likely than were men to die (3.3% vs. 4.3%) or be hospitalized (49.1% vs. 52.3%) after an ED visit for CVD. The difference may be due to women’s generally lower-risk diagnoses, Dr. Mamas said, but there could be an underestimation of deaths in women.
In logistic regression models adjusted for baseline covariates, women with intracranial hemorrhage (ICH) had a higher risk of being admitted to hospital or dying compared with men with ICH.
Men were more likely to die if they presented with hypertensive heart or kidney disease, AF/flutter, AMI or cardiac arrest, the researchers found.
“We did not track deaths outside of the hospital setting,” Dr. Mamas pointed out. Given past evidence that women are more likely to be inappropriately discharged from the ED, and strong evidence for the systemic undertreatment of women, further study is warranted to track outcomes beyond the ED visit,” he added.
The researchers called for further research into understanding the underlying factors driving the differences in CVD patterns and outcomes between men and women.
Reached for comment, Maryann McLaughlin, MD, a cardiologist at Mount Sinai Hospital, New York, said: “Hypertension is a silent killer” and this study “reiterates that people need to get their blood pressure checked more regularly.
“In the very least, if they do present to the hospital as not feeling well or whatever it is, and they are identified as having high blood pressure, that’s an important opportunity to really teach them about hypertension and have them follow-up with it,” Dr. McLaughlin told this news organization.
The study was supported by Health Data Research UK. Dr. Keele and Dr. McLaughlin have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A look at the top cardiovascular disease (CVD) diagnoses in U.S. emergency departments (EDs) suggests that many heart-related emergencies are due to poorly controlled high blood pressure.
In a study of more than 20 million ED visits, about one-third of CVD-related ED visits in the United States were for hypertension-related conditions.
Overall, 13% of ED visits, representing more than 2.7 million individuals, were for essential hypertension.
The fact that these visits rarely led to an inpatient admission (< 3%) or death (< 0.1%) suggests they were “mostly related to the management of hypertension,” lead author Mamas A. Mamas, MD, Keele University, Staffordshire, England, said in a news release.
The study was published online in the Journal of the American Heart Association.
Nationwide sample
The researchers studied more than 20.6 million ED encounters in adults with a primary CVD diagnosis using data from the Nationwide Emergency Department Sample between 2016 and 2018.
In the sample, 49% were women, and the median age was 67 years. Men had poorer overall baseline cardiometabolic profiles, but women had higher rates of obesity, hypertension, and cerebrovascular disease. The majority had Medicare or Medicaid insurance.
In women, essential hypertension was the most common reason for an ED visit (16%), followed by hypertensive heart or kidney disease (14%) and atrial fibrillation (AF)/flutter (10%).
In men, the top three reasons were hypertensive heart or kidney disease (15%), essential hypertension (11%), and acute myocardial infarction (AMI, 11%).
On presentation, women were significantly more likely to have essential hypertension, hypertensive crisis, AF/flutter, supraventricular tachycardia, pulmonary embolism, or ischemic stroke, while men were more likely to have AMI, or cardiac arrest.
“Previous studies have shown sex differences in patterns of CVD among hospitalized patients,” Dr. Mamas noted. “However, examining CVD encounters in the ED provides a more complete picture of the cardiovascular healthcare needs of men and women, as it captures encounters prior to hospitalization.”
He noted that previous studies of CVD emergency visits are limited to suspected MI visits. “Therefore, this analysis of 15 CVD conditions helps to better understand the full spectrum of acute CVD needs, including sex disparities in hospitalization and risk of death,” Dr. Mamas said.
Sex differences in outcomes
The study found that outcomes from the emergency CVD visits were slightly different for men and women.
Overall, women were less likely than were men to die (3.3% vs. 4.3%) or be hospitalized (49.1% vs. 52.3%) after an ED visit for CVD. The difference may be due to women’s generally lower-risk diagnoses, Dr. Mamas said, but there could be an underestimation of deaths in women.
In logistic regression models adjusted for baseline covariates, women with intracranial hemorrhage (ICH) had a higher risk of being admitted to hospital or dying compared with men with ICH.
Men were more likely to die if they presented with hypertensive heart or kidney disease, AF/flutter, AMI or cardiac arrest, the researchers found.
“We did not track deaths outside of the hospital setting,” Dr. Mamas pointed out. Given past evidence that women are more likely to be inappropriately discharged from the ED, and strong evidence for the systemic undertreatment of women, further study is warranted to track outcomes beyond the ED visit,” he added.
The researchers called for further research into understanding the underlying factors driving the differences in CVD patterns and outcomes between men and women.
Reached for comment, Maryann McLaughlin, MD, a cardiologist at Mount Sinai Hospital, New York, said: “Hypertension is a silent killer” and this study “reiterates that people need to get their blood pressure checked more regularly.
“In the very least, if they do present to the hospital as not feeling well or whatever it is, and they are identified as having high blood pressure, that’s an important opportunity to really teach them about hypertension and have them follow-up with it,” Dr. McLaughlin told this news organization.
The study was supported by Health Data Research UK. Dr. Keele and Dr. McLaughlin have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Add PCSK9 inhibitor to high-intensity statin at primary PCI, proposes sham-controlled EPIC-STEMI
It’s best to have patients on aggressive lipid-lowering therapy before discharge after an acute ST-segment elevation myocardial infarction (STEMI), so why not start it right away – even in the cath lab – using some of the most potent LDL cholesterol–lowering agents available?
That was a main idea behind the randomized, sham-controlled EPIC-STEMI trial, in which STEMI patients were started on a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor immediately before direct percutaneous coronary intervention (PCI) and on top of high-intensity statins.
Those in the trial getting the active agent showed a 22% drop in LDL cholesterol levels by 6 weeks, compared with the control group given a sham injection along with high-intensity statins. They were also more likely to meet LDL cholesterol goals specified in some guidelines, including reduction by at least 50%. And those outcomes were achieved regardless of baseline LDL cholesterol levels or prior statin use.
Adoption of the trial’s early, aggressive LDL cholesterolreduction strategy in practice “has the potential to substantially reduce morbidity and mortality” in such cases “by further reducing LDL beyond statins in a much greater number of high-risk patients than are currently being treated with these agents,” suggested principal investigator Shamir R. Mehta, MD, MSc, when presenting the findings at the Transcatheter Cardiovascular Therapeutics annual meeting, sponsored by the Cardiovascular Research Foundation.
Adherence to secondary prevention measures in patients with acute coronary syndromes (ACS) is much better if they are started before hospital discharge, explained Dr. Mehta, senior scientist with Population Health Research Institute and professor of medicine at McMaster University, Hamilton, Ont. But “as soon as the patient has left the hospital, it is much more difficult to get these therapies on board.”
Routine adoption of such aggressive in-hospital, lipid-lowering therapy for the vast population with ACS would likely mean far fewer deaths and cardiovascular events “across a broader patient population.”
EPIC-STEMI is among the first studies to explore the strategy. “I think that’s the point of the trial that we wanted to make, that we don’t yet have data on this. We’re treading very carefully with PCSK9 inhibitors, and it’s just inching forward in populations. And I think we need a bold trial to see whether or not this changes things.”
The PCSK9 inhibitor alirocumab (Praluent) was used in EPIC-STEMI, which was published in EuroIntervention, with Dr. Mehta as lead author, the same day as his presentation. The drug and its sham injection were given on top of either atorvastatin 40-80 mg or rosuvastatin 40 mg.
Early initiation of statins in patients with acute STEMI has become standard, but there’s good evidence from intracoronary imaging studies suggesting that the addition of PCSK9 inhibitors might promote further stabilization of plaques that could potentially cause recurrent ischemic events.
Treatment with the injectable drugs plus statins led to significant coronary lesion regression in the GLAGOV trial of patients with stable coronary disease. And initiation of PCSK9 inhibitors with high-intensity statins soon after PCI for ACS improved atheroma shrinkage in non–infarct-related arteries over 1 year in the recent, placebo-controlled PACMAN-AMI trial.
Dr. Mehta pointed out that LDL reductions on PCSK9 inhibition, compared with the sham control, weren’t necessarily as impressive as might be expected from the major trials of long-term therapy with the drugs.
“You need longer [therapy] in order to see a difference in LDL levels when you use a PCSK9 inhibitor acutely. This is shown also on measures of infarct size.” There was no difference between treatment groups in infarct size as measured by levels of the MB fraction of creatine kinase, he reported.
“What this is telling us is that the acute use of a PCSK9 inhibitor did not modify the size or the severity of the baseline STEMI event.”
And EPIC-STEMI was too small and never intended to assess clinical outcomes; it was more about feasibility and what degree of LDL cholesterol lowering might be expected.
The trial was needed, Dr. Mehta said, because the PCSK9 inhibitors haven’t been extensively adopted into clinical practice and are not getting to the patients who could most benefit. One of the reasons for that is quite clear to him. “We are missing the high-risk patients because we are not treating them acutely,” Dr. Mehta said in an interview.
The strategy “has not yet been evaluated, and there have been barriers,” he observed. “Cost has been a barrier. Access to the drug has been a barrier. But in terms of the science, in terms of reducing cardiovascular events, this is a strategy that has to be tested.”
The aggressive, early LDL cholesterol reduction strategy should be evaluated for its effect on long-term outcomes, “especially knowing that in the first 30 days to 6 months post STEMI there’s a tremendous uptick in ischemic events, including recurrent myocardial infarction,” Roxana Mehran, MD, said at a media briefing on EPIC-STEMI held before Dr. Mehta’s formal presentation.
The “fantastic reduction acutely” with a PCSK9 inhibitor on top of statins, “hopefully reducing inflammation” similarly to what’s been observed in past trials, “absolutely warrants” a STEMI clinical outcomes trial, said Dr. Mehran, Icahn School of Medicine at Mount Sinai, New York, who isn’t connected with EPIC-STEMI.
If better post-discharge medication adherence is one of the acute strategy’s goals, it will be important to consider the potential influence of prescribing a periodically injected drug, proposed Eric A. Cohen, MD, Sunnybrook Health Sciences Center, Toronto, at the press conference.
“Keep in mind that STEMI patients typically come to the hospital on zero medications and leave 2 days later on five medications,” Dr. Cohen observed. “I’m curious whether having one of those as a sub-Q injection every 2 weeks, and reducing the pill burden, will help or deter adherence to therapy. I think it’s worth studying.”
The trial originally included 97 patients undergoing PCI for STEMI who were randomly assigned to receive the PCSK9 inhibitor or a sham injection on top of high-intensity statins, without regard to LDL cholesterol levels. Randomization took place after diagnostic angiography but before PCI.
The analysis, however, subsequently excluded 29 patients who could not continue with the study, “mainly because of hospital research clinic closure due to the COVID-19 pandemic,” the published report states.
That left 68 patients who had received at least one dose of PCSK9 inhibitor, alirocumab 150 mg subcutaneously, or the sham injection, and had at least one blood draw for LDL cholesterol response which, Dr. Mehta said, still left adequate statistical power for the LDL cholesterol–based primary endpoint.
By 6 weeks, LDL cholesterol levels had fallen 72.9% in the active-therapy group and by 48.1% in the control group (P < .001). Also, 92.1% and 56.7% of patients, respectively (P = .002), had achieved levels below the 1.4 mmol/L (54 mg/dL) goal in the European guidelines, Dr. Mehta reported.
Levels fell more than 50% compared with baseline in 89.5% of alirocumab patients and 60% (P = .007) of controls, respectively.
There was no significant difference in rates of attaining LDL cholesterol levels below the 70 mg/dL (1.8 mmol/L) threshold specified in U.S. guidelines for very high-risk patients: 94.7% of alirocumab patients and 83.4% of controls (P = .26).
Nor did the groups differ significantly in natriuretic peptide levels, which reflect ventricular remodeling; or in 6-week change in the inflammatory biomarker high-sensitivity C-reactive protein.
An open-label, randomized trial scheduled to launch before the end of 2022 will explore similarly early initiation of a PCSK9 inhibitor, compared with standard lipid management, in an estimated 4,000 patients hospitalized with STEMI or non-STEMI.
The EVOLVE MI trial is looking at the monoclonal antibody evolocumab (Repatha) for its effect on the primary endpoint of myocardial infarction, ischemic stroke, arterial revascularization, or death from any cause over an expected 3-4 years.
EPIC-STEMI was supported in part by Sanofi. Dr. Mehta reported an unrestricted grant from Sanofi to Hamilton Health Sciences for the present study and consulting fees from Amgen, Sanofi, and Novartis. Dr. Cohen disclosed receiving grant support from and holding research contracts with Abbott Vascular; and receiving fees for consulting, honoraria, or serving on a speaker’s bureau for Abbott Vascular, Medtronic, and Baylis. Dr. Mehran disclosed receiving grants or research support from numerous pharmaceutical companies; receiving consultant fee or honoraria or serving on a speaker’s bureau for Novartis, Abbott Vascular, Janssen, Medtronic, Medscape/WebMD, and Cine-Med Research; and holding equity, stock, or stock options with Control Rad, Applied Therapeutics, and Elixir Medical.
A version of this article first appeared on Medscape.com.
It’s best to have patients on aggressive lipid-lowering therapy before discharge after an acute ST-segment elevation myocardial infarction (STEMI), so why not start it right away – even in the cath lab – using some of the most potent LDL cholesterol–lowering agents available?
That was a main idea behind the randomized, sham-controlled EPIC-STEMI trial, in which STEMI patients were started on a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor immediately before direct percutaneous coronary intervention (PCI) and on top of high-intensity statins.
Those in the trial getting the active agent showed a 22% drop in LDL cholesterol levels by 6 weeks, compared with the control group given a sham injection along with high-intensity statins. They were also more likely to meet LDL cholesterol goals specified in some guidelines, including reduction by at least 50%. And those outcomes were achieved regardless of baseline LDL cholesterol levels or prior statin use.
Adoption of the trial’s early, aggressive LDL cholesterolreduction strategy in practice “has the potential to substantially reduce morbidity and mortality” in such cases “by further reducing LDL beyond statins in a much greater number of high-risk patients than are currently being treated with these agents,” suggested principal investigator Shamir R. Mehta, MD, MSc, when presenting the findings at the Transcatheter Cardiovascular Therapeutics annual meeting, sponsored by the Cardiovascular Research Foundation.
Adherence to secondary prevention measures in patients with acute coronary syndromes (ACS) is much better if they are started before hospital discharge, explained Dr. Mehta, senior scientist with Population Health Research Institute and professor of medicine at McMaster University, Hamilton, Ont. But “as soon as the patient has left the hospital, it is much more difficult to get these therapies on board.”
Routine adoption of such aggressive in-hospital, lipid-lowering therapy for the vast population with ACS would likely mean far fewer deaths and cardiovascular events “across a broader patient population.”
EPIC-STEMI is among the first studies to explore the strategy. “I think that’s the point of the trial that we wanted to make, that we don’t yet have data on this. We’re treading very carefully with PCSK9 inhibitors, and it’s just inching forward in populations. And I think we need a bold trial to see whether or not this changes things.”
The PCSK9 inhibitor alirocumab (Praluent) was used in EPIC-STEMI, which was published in EuroIntervention, with Dr. Mehta as lead author, the same day as his presentation. The drug and its sham injection were given on top of either atorvastatin 40-80 mg or rosuvastatin 40 mg.
Early initiation of statins in patients with acute STEMI has become standard, but there’s good evidence from intracoronary imaging studies suggesting that the addition of PCSK9 inhibitors might promote further stabilization of plaques that could potentially cause recurrent ischemic events.
Treatment with the injectable drugs plus statins led to significant coronary lesion regression in the GLAGOV trial of patients with stable coronary disease. And initiation of PCSK9 inhibitors with high-intensity statins soon after PCI for ACS improved atheroma shrinkage in non–infarct-related arteries over 1 year in the recent, placebo-controlled PACMAN-AMI trial.
Dr. Mehta pointed out that LDL reductions on PCSK9 inhibition, compared with the sham control, weren’t necessarily as impressive as might be expected from the major trials of long-term therapy with the drugs.
“You need longer [therapy] in order to see a difference in LDL levels when you use a PCSK9 inhibitor acutely. This is shown also on measures of infarct size.” There was no difference between treatment groups in infarct size as measured by levels of the MB fraction of creatine kinase, he reported.
“What this is telling us is that the acute use of a PCSK9 inhibitor did not modify the size or the severity of the baseline STEMI event.”
And EPIC-STEMI was too small and never intended to assess clinical outcomes; it was more about feasibility and what degree of LDL cholesterol lowering might be expected.
The trial was needed, Dr. Mehta said, because the PCSK9 inhibitors haven’t been extensively adopted into clinical practice and are not getting to the patients who could most benefit. One of the reasons for that is quite clear to him. “We are missing the high-risk patients because we are not treating them acutely,” Dr. Mehta said in an interview.
The strategy “has not yet been evaluated, and there have been barriers,” he observed. “Cost has been a barrier. Access to the drug has been a barrier. But in terms of the science, in terms of reducing cardiovascular events, this is a strategy that has to be tested.”
The aggressive, early LDL cholesterol reduction strategy should be evaluated for its effect on long-term outcomes, “especially knowing that in the first 30 days to 6 months post STEMI there’s a tremendous uptick in ischemic events, including recurrent myocardial infarction,” Roxana Mehran, MD, said at a media briefing on EPIC-STEMI held before Dr. Mehta’s formal presentation.
The “fantastic reduction acutely” with a PCSK9 inhibitor on top of statins, “hopefully reducing inflammation” similarly to what’s been observed in past trials, “absolutely warrants” a STEMI clinical outcomes trial, said Dr. Mehran, Icahn School of Medicine at Mount Sinai, New York, who isn’t connected with EPIC-STEMI.
If better post-discharge medication adherence is one of the acute strategy’s goals, it will be important to consider the potential influence of prescribing a periodically injected drug, proposed Eric A. Cohen, MD, Sunnybrook Health Sciences Center, Toronto, at the press conference.
“Keep in mind that STEMI patients typically come to the hospital on zero medications and leave 2 days later on five medications,” Dr. Cohen observed. “I’m curious whether having one of those as a sub-Q injection every 2 weeks, and reducing the pill burden, will help or deter adherence to therapy. I think it’s worth studying.”
The trial originally included 97 patients undergoing PCI for STEMI who were randomly assigned to receive the PCSK9 inhibitor or a sham injection on top of high-intensity statins, without regard to LDL cholesterol levels. Randomization took place after diagnostic angiography but before PCI.
The analysis, however, subsequently excluded 29 patients who could not continue with the study, “mainly because of hospital research clinic closure due to the COVID-19 pandemic,” the published report states.
That left 68 patients who had received at least one dose of PCSK9 inhibitor, alirocumab 150 mg subcutaneously, or the sham injection, and had at least one blood draw for LDL cholesterol response which, Dr. Mehta said, still left adequate statistical power for the LDL cholesterol–based primary endpoint.
By 6 weeks, LDL cholesterol levels had fallen 72.9% in the active-therapy group and by 48.1% in the control group (P < .001). Also, 92.1% and 56.7% of patients, respectively (P = .002), had achieved levels below the 1.4 mmol/L (54 mg/dL) goal in the European guidelines, Dr. Mehta reported.
Levels fell more than 50% compared with baseline in 89.5% of alirocumab patients and 60% (P = .007) of controls, respectively.
There was no significant difference in rates of attaining LDL cholesterol levels below the 70 mg/dL (1.8 mmol/L) threshold specified in U.S. guidelines for very high-risk patients: 94.7% of alirocumab patients and 83.4% of controls (P = .26).
Nor did the groups differ significantly in natriuretic peptide levels, which reflect ventricular remodeling; or in 6-week change in the inflammatory biomarker high-sensitivity C-reactive protein.
An open-label, randomized trial scheduled to launch before the end of 2022 will explore similarly early initiation of a PCSK9 inhibitor, compared with standard lipid management, in an estimated 4,000 patients hospitalized with STEMI or non-STEMI.
The EVOLVE MI trial is looking at the monoclonal antibody evolocumab (Repatha) for its effect on the primary endpoint of myocardial infarction, ischemic stroke, arterial revascularization, or death from any cause over an expected 3-4 years.
EPIC-STEMI was supported in part by Sanofi. Dr. Mehta reported an unrestricted grant from Sanofi to Hamilton Health Sciences for the present study and consulting fees from Amgen, Sanofi, and Novartis. Dr. Cohen disclosed receiving grant support from and holding research contracts with Abbott Vascular; and receiving fees for consulting, honoraria, or serving on a speaker’s bureau for Abbott Vascular, Medtronic, and Baylis. Dr. Mehran disclosed receiving grants or research support from numerous pharmaceutical companies; receiving consultant fee or honoraria or serving on a speaker’s bureau for Novartis, Abbott Vascular, Janssen, Medtronic, Medscape/WebMD, and Cine-Med Research; and holding equity, stock, or stock options with Control Rad, Applied Therapeutics, and Elixir Medical.
A version of this article first appeared on Medscape.com.
It’s best to have patients on aggressive lipid-lowering therapy before discharge after an acute ST-segment elevation myocardial infarction (STEMI), so why not start it right away – even in the cath lab – using some of the most potent LDL cholesterol–lowering agents available?
That was a main idea behind the randomized, sham-controlled EPIC-STEMI trial, in which STEMI patients were started on a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor immediately before direct percutaneous coronary intervention (PCI) and on top of high-intensity statins.
Those in the trial getting the active agent showed a 22% drop in LDL cholesterol levels by 6 weeks, compared with the control group given a sham injection along with high-intensity statins. They were also more likely to meet LDL cholesterol goals specified in some guidelines, including reduction by at least 50%. And those outcomes were achieved regardless of baseline LDL cholesterol levels or prior statin use.
Adoption of the trial’s early, aggressive LDL cholesterolreduction strategy in practice “has the potential to substantially reduce morbidity and mortality” in such cases “by further reducing LDL beyond statins in a much greater number of high-risk patients than are currently being treated with these agents,” suggested principal investigator Shamir R. Mehta, MD, MSc, when presenting the findings at the Transcatheter Cardiovascular Therapeutics annual meeting, sponsored by the Cardiovascular Research Foundation.
Adherence to secondary prevention measures in patients with acute coronary syndromes (ACS) is much better if they are started before hospital discharge, explained Dr. Mehta, senior scientist with Population Health Research Institute and professor of medicine at McMaster University, Hamilton, Ont. But “as soon as the patient has left the hospital, it is much more difficult to get these therapies on board.”
Routine adoption of such aggressive in-hospital, lipid-lowering therapy for the vast population with ACS would likely mean far fewer deaths and cardiovascular events “across a broader patient population.”
EPIC-STEMI is among the first studies to explore the strategy. “I think that’s the point of the trial that we wanted to make, that we don’t yet have data on this. We’re treading very carefully with PCSK9 inhibitors, and it’s just inching forward in populations. And I think we need a bold trial to see whether or not this changes things.”
The PCSK9 inhibitor alirocumab (Praluent) was used in EPIC-STEMI, which was published in EuroIntervention, with Dr. Mehta as lead author, the same day as his presentation. The drug and its sham injection were given on top of either atorvastatin 40-80 mg or rosuvastatin 40 mg.
Early initiation of statins in patients with acute STEMI has become standard, but there’s good evidence from intracoronary imaging studies suggesting that the addition of PCSK9 inhibitors might promote further stabilization of plaques that could potentially cause recurrent ischemic events.
Treatment with the injectable drugs plus statins led to significant coronary lesion regression in the GLAGOV trial of patients with stable coronary disease. And initiation of PCSK9 inhibitors with high-intensity statins soon after PCI for ACS improved atheroma shrinkage in non–infarct-related arteries over 1 year in the recent, placebo-controlled PACMAN-AMI trial.
Dr. Mehta pointed out that LDL reductions on PCSK9 inhibition, compared with the sham control, weren’t necessarily as impressive as might be expected from the major trials of long-term therapy with the drugs.
“You need longer [therapy] in order to see a difference in LDL levels when you use a PCSK9 inhibitor acutely. This is shown also on measures of infarct size.” There was no difference between treatment groups in infarct size as measured by levels of the MB fraction of creatine kinase, he reported.
“What this is telling us is that the acute use of a PCSK9 inhibitor did not modify the size or the severity of the baseline STEMI event.”
And EPIC-STEMI was too small and never intended to assess clinical outcomes; it was more about feasibility and what degree of LDL cholesterol lowering might be expected.
The trial was needed, Dr. Mehta said, because the PCSK9 inhibitors haven’t been extensively adopted into clinical practice and are not getting to the patients who could most benefit. One of the reasons for that is quite clear to him. “We are missing the high-risk patients because we are not treating them acutely,” Dr. Mehta said in an interview.
The strategy “has not yet been evaluated, and there have been barriers,” he observed. “Cost has been a barrier. Access to the drug has been a barrier. But in terms of the science, in terms of reducing cardiovascular events, this is a strategy that has to be tested.”
The aggressive, early LDL cholesterol reduction strategy should be evaluated for its effect on long-term outcomes, “especially knowing that in the first 30 days to 6 months post STEMI there’s a tremendous uptick in ischemic events, including recurrent myocardial infarction,” Roxana Mehran, MD, said at a media briefing on EPIC-STEMI held before Dr. Mehta’s formal presentation.
The “fantastic reduction acutely” with a PCSK9 inhibitor on top of statins, “hopefully reducing inflammation” similarly to what’s been observed in past trials, “absolutely warrants” a STEMI clinical outcomes trial, said Dr. Mehran, Icahn School of Medicine at Mount Sinai, New York, who isn’t connected with EPIC-STEMI.
If better post-discharge medication adherence is one of the acute strategy’s goals, it will be important to consider the potential influence of prescribing a periodically injected drug, proposed Eric A. Cohen, MD, Sunnybrook Health Sciences Center, Toronto, at the press conference.
“Keep in mind that STEMI patients typically come to the hospital on zero medications and leave 2 days later on five medications,” Dr. Cohen observed. “I’m curious whether having one of those as a sub-Q injection every 2 weeks, and reducing the pill burden, will help or deter adherence to therapy. I think it’s worth studying.”
The trial originally included 97 patients undergoing PCI for STEMI who were randomly assigned to receive the PCSK9 inhibitor or a sham injection on top of high-intensity statins, without regard to LDL cholesterol levels. Randomization took place after diagnostic angiography but before PCI.
The analysis, however, subsequently excluded 29 patients who could not continue with the study, “mainly because of hospital research clinic closure due to the COVID-19 pandemic,” the published report states.
That left 68 patients who had received at least one dose of PCSK9 inhibitor, alirocumab 150 mg subcutaneously, or the sham injection, and had at least one blood draw for LDL cholesterol response which, Dr. Mehta said, still left adequate statistical power for the LDL cholesterol–based primary endpoint.
By 6 weeks, LDL cholesterol levels had fallen 72.9% in the active-therapy group and by 48.1% in the control group (P < .001). Also, 92.1% and 56.7% of patients, respectively (P = .002), had achieved levels below the 1.4 mmol/L (54 mg/dL) goal in the European guidelines, Dr. Mehta reported.
Levels fell more than 50% compared with baseline in 89.5% of alirocumab patients and 60% (P = .007) of controls, respectively.
There was no significant difference in rates of attaining LDL cholesterol levels below the 70 mg/dL (1.8 mmol/L) threshold specified in U.S. guidelines for very high-risk patients: 94.7% of alirocumab patients and 83.4% of controls (P = .26).
Nor did the groups differ significantly in natriuretic peptide levels, which reflect ventricular remodeling; or in 6-week change in the inflammatory biomarker high-sensitivity C-reactive protein.
An open-label, randomized trial scheduled to launch before the end of 2022 will explore similarly early initiation of a PCSK9 inhibitor, compared with standard lipid management, in an estimated 4,000 patients hospitalized with STEMI or non-STEMI.
The EVOLVE MI trial is looking at the monoclonal antibody evolocumab (Repatha) for its effect on the primary endpoint of myocardial infarction, ischemic stroke, arterial revascularization, or death from any cause over an expected 3-4 years.
EPIC-STEMI was supported in part by Sanofi. Dr. Mehta reported an unrestricted grant from Sanofi to Hamilton Health Sciences for the present study and consulting fees from Amgen, Sanofi, and Novartis. Dr. Cohen disclosed receiving grant support from and holding research contracts with Abbott Vascular; and receiving fees for consulting, honoraria, or serving on a speaker’s bureau for Abbott Vascular, Medtronic, and Baylis. Dr. Mehran disclosed receiving grants or research support from numerous pharmaceutical companies; receiving consultant fee or honoraria or serving on a speaker’s bureau for Novartis, Abbott Vascular, Janssen, Medtronic, Medscape/WebMD, and Cine-Med Research; and holding equity, stock, or stock options with Control Rad, Applied Therapeutics, and Elixir Medical.
A version of this article first appeared on Medscape.com.
FROM TCT 2022
Post-PCI FFR in multivessel disease predicts target vessel failure: FAME 3 analysis
Risk by FFR is continuous variable
In a new analysis of the previously published FAME 3 trial, which compared fractional flow reserve–guided percutaneous coronary interventions to coronary artery bypass surgery (CABG) in patients with three-vessel disease, post-PCI FFR was shown to predict both target vessel failure (TVF) and risk of cardiac events.
“We found that the post-PCI FFR had prognostic value both for the vessel and for the patient,” reported Zsolt Piroth, MD, PhD, deputy head, adult cardiology, György Gottsegen Institute of Cardiology, Budapest.
In this post hoc analysis, which was not a prespecified FAME 3 substudy, the goal was to look at the prognostic value of both post-PCI FFR and intravascular ultrasound, which were recommended in the study protocol. Several studies have addressed the value of these measures previously, according to Dr. Piroth, but he said the clinical value “has remained poorly defined” despite the currently available data.
The FAME 3 trial, published in the New England Journal of Medicine, was negative. It failed to confirm the study hypothesis that FFR-guided PCI is noninferior to CABG for the outcome of major adverse cardiac events (MACE) at 12 months.
However, this multinational trial has generated a large body of data with which to explore other issues relevant to revascularization. In this analysis, the goal was to evaluate whether post-PCI FFR predicted outcomes in complex multivessel revascularizations as it has been shown previously to do in single-vessel disease.
Presented at the Transcatheter Cardiovascular Therapeutics annual meeting, the focus of this analysis was on the 461 (61%) of patients in the 757-patient PCI arm of FAME 3 who underwent post-PCI FFR. The authors also looked at the predictive value of intravascular ultrasound, even though this was performed in just 11% of this group of trial participants.
As a continuous value, each 0.1-unit change in the post-PCI FFR was found to be prognostically significant for the outcome of TVF, defined as a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization (only postprocedural events were counted in this analysis). Specifically, for each 0.1-unit increase on a univariate analysis, the risk of TVF was reduced by about one-third (hazard ratio, 0.67; P = .0165).
On a patient level, a 0.1-unit increase in lowest post-PCI FFR of any assessed vessel was also associated with the same relative risk reduction (HR, 0.65; P = .0074) in the outcomes of cardiac death, target vessel MI, or target vessel revascularization, according to Dr. Piroth. On a receiver operating characteristic curve analysis, a value of 0.88 or below was predictive of TVF.
Although several other patient characteristics were also risk predictors of TVF on univariate analysis, only renal disease and the single lowest post-PCI FFR (as a continuous variable) emerged as predictors of TVF on multivariable analysis after adjustment for key clinical parameters, Dr. Piroth reported.
The reason why post-PCI FFR was not performed in almost 40% of patients randomized to PCI is unclear, but Dr. Piroth reported that the baseline characteristics of those who were or were not assessed with FFR after their procedure did not differ to any major degree.
Despite “a trend for improved outcomes in those who underwent post-PCI FFR,” Dr. Piroth, whose substudy was published in Circulation: Cardiovascular Interventions simultaneously with his TCT presentation, acknowledged that the reasons for a potential benefit cannot be derived from this post hoc analysis.
As for the prognostic value of IVUS, any conclusions are limited by the small proportion of patients who underwent this form of imaging. Overall, IVUS imaging was associated with longer procedures and more stents and “if anything, a signal for harm” in this analysis, but Dr. Piroth cautioned against any conclusions because of the small data pool.
The prognostic value of post-PCI FFR in complex multivessel disease is supported by these data, but the analysis was not designed to determine whether post-PCI FFR has relevance to intervention.
According to J. Dawn Abbott, MD, an FFR analysis conducted to identify lesions that are candidates for treatment should not be confused with FFR for physiologically guided PCI to optimize outcomes.
Noting that post-PCI FFR was encouraged in this study but not mandated and that these FFR values did not typically or necessarily lead to a change in management, take home messages about the value of post-PCI FFR in multivessel disease remain limited, said Dr. Abbott, director of interventional cardiology fellowship training, Brown University, Providence, R.I.
“There was a trend toward improved outcomes in patients who had this measurement done, but, unfortunately, we do not have data regarding whether these patients had further interventions performed,” Dr. Piroth acknowledged.
The post-PCI FFR values were made available to the treating physicians, but Dr. Piroth reiterated that it is unknown whether the physicians considered this information actionable. Moreover, “the vast majority had a nonsignificant post-PCI FFR” result, and “all of the patients had an angiographically successful PCI,” Dr. Piroth added.
Dr. Piroth has financial relationships with Abbott Vascular and Boston Scientific. Dr. Abbott reports financial relationships with Abbott Vascular, Boston Scientific, Medtronic, Microport, Philips, Penumbra, Recor, and Shockwave.
Risk by FFR is continuous variable
Risk by FFR is continuous variable
In a new analysis of the previously published FAME 3 trial, which compared fractional flow reserve–guided percutaneous coronary interventions to coronary artery bypass surgery (CABG) in patients with three-vessel disease, post-PCI FFR was shown to predict both target vessel failure (TVF) and risk of cardiac events.
“We found that the post-PCI FFR had prognostic value both for the vessel and for the patient,” reported Zsolt Piroth, MD, PhD, deputy head, adult cardiology, György Gottsegen Institute of Cardiology, Budapest.
In this post hoc analysis, which was not a prespecified FAME 3 substudy, the goal was to look at the prognostic value of both post-PCI FFR and intravascular ultrasound, which were recommended in the study protocol. Several studies have addressed the value of these measures previously, according to Dr. Piroth, but he said the clinical value “has remained poorly defined” despite the currently available data.
The FAME 3 trial, published in the New England Journal of Medicine, was negative. It failed to confirm the study hypothesis that FFR-guided PCI is noninferior to CABG for the outcome of major adverse cardiac events (MACE) at 12 months.
However, this multinational trial has generated a large body of data with which to explore other issues relevant to revascularization. In this analysis, the goal was to evaluate whether post-PCI FFR predicted outcomes in complex multivessel revascularizations as it has been shown previously to do in single-vessel disease.
Presented at the Transcatheter Cardiovascular Therapeutics annual meeting, the focus of this analysis was on the 461 (61%) of patients in the 757-patient PCI arm of FAME 3 who underwent post-PCI FFR. The authors also looked at the predictive value of intravascular ultrasound, even though this was performed in just 11% of this group of trial participants.
As a continuous value, each 0.1-unit change in the post-PCI FFR was found to be prognostically significant for the outcome of TVF, defined as a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization (only postprocedural events were counted in this analysis). Specifically, for each 0.1-unit increase on a univariate analysis, the risk of TVF was reduced by about one-third (hazard ratio, 0.67; P = .0165).
On a patient level, a 0.1-unit increase in lowest post-PCI FFR of any assessed vessel was also associated with the same relative risk reduction (HR, 0.65; P = .0074) in the outcomes of cardiac death, target vessel MI, or target vessel revascularization, according to Dr. Piroth. On a receiver operating characteristic curve analysis, a value of 0.88 or below was predictive of TVF.
Although several other patient characteristics were also risk predictors of TVF on univariate analysis, only renal disease and the single lowest post-PCI FFR (as a continuous variable) emerged as predictors of TVF on multivariable analysis after adjustment for key clinical parameters, Dr. Piroth reported.
The reason why post-PCI FFR was not performed in almost 40% of patients randomized to PCI is unclear, but Dr. Piroth reported that the baseline characteristics of those who were or were not assessed with FFR after their procedure did not differ to any major degree.
Despite “a trend for improved outcomes in those who underwent post-PCI FFR,” Dr. Piroth, whose substudy was published in Circulation: Cardiovascular Interventions simultaneously with his TCT presentation, acknowledged that the reasons for a potential benefit cannot be derived from this post hoc analysis.
As for the prognostic value of IVUS, any conclusions are limited by the small proportion of patients who underwent this form of imaging. Overall, IVUS imaging was associated with longer procedures and more stents and “if anything, a signal for harm” in this analysis, but Dr. Piroth cautioned against any conclusions because of the small data pool.
The prognostic value of post-PCI FFR in complex multivessel disease is supported by these data, but the analysis was not designed to determine whether post-PCI FFR has relevance to intervention.
According to J. Dawn Abbott, MD, an FFR analysis conducted to identify lesions that are candidates for treatment should not be confused with FFR for physiologically guided PCI to optimize outcomes.
Noting that post-PCI FFR was encouraged in this study but not mandated and that these FFR values did not typically or necessarily lead to a change in management, take home messages about the value of post-PCI FFR in multivessel disease remain limited, said Dr. Abbott, director of interventional cardiology fellowship training, Brown University, Providence, R.I.
“There was a trend toward improved outcomes in patients who had this measurement done, but, unfortunately, we do not have data regarding whether these patients had further interventions performed,” Dr. Piroth acknowledged.
The post-PCI FFR values were made available to the treating physicians, but Dr. Piroth reiterated that it is unknown whether the physicians considered this information actionable. Moreover, “the vast majority had a nonsignificant post-PCI FFR” result, and “all of the patients had an angiographically successful PCI,” Dr. Piroth added.
Dr. Piroth has financial relationships with Abbott Vascular and Boston Scientific. Dr. Abbott reports financial relationships with Abbott Vascular, Boston Scientific, Medtronic, Microport, Philips, Penumbra, Recor, and Shockwave.
In a new analysis of the previously published FAME 3 trial, which compared fractional flow reserve–guided percutaneous coronary interventions to coronary artery bypass surgery (CABG) in patients with three-vessel disease, post-PCI FFR was shown to predict both target vessel failure (TVF) and risk of cardiac events.
“We found that the post-PCI FFR had prognostic value both for the vessel and for the patient,” reported Zsolt Piroth, MD, PhD, deputy head, adult cardiology, György Gottsegen Institute of Cardiology, Budapest.
In this post hoc analysis, which was not a prespecified FAME 3 substudy, the goal was to look at the prognostic value of both post-PCI FFR and intravascular ultrasound, which were recommended in the study protocol. Several studies have addressed the value of these measures previously, according to Dr. Piroth, but he said the clinical value “has remained poorly defined” despite the currently available data.
The FAME 3 trial, published in the New England Journal of Medicine, was negative. It failed to confirm the study hypothesis that FFR-guided PCI is noninferior to CABG for the outcome of major adverse cardiac events (MACE) at 12 months.
However, this multinational trial has generated a large body of data with which to explore other issues relevant to revascularization. In this analysis, the goal was to evaluate whether post-PCI FFR predicted outcomes in complex multivessel revascularizations as it has been shown previously to do in single-vessel disease.
Presented at the Transcatheter Cardiovascular Therapeutics annual meeting, the focus of this analysis was on the 461 (61%) of patients in the 757-patient PCI arm of FAME 3 who underwent post-PCI FFR. The authors also looked at the predictive value of intravascular ultrasound, even though this was performed in just 11% of this group of trial participants.
As a continuous value, each 0.1-unit change in the post-PCI FFR was found to be prognostically significant for the outcome of TVF, defined as a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization (only postprocedural events were counted in this analysis). Specifically, for each 0.1-unit increase on a univariate analysis, the risk of TVF was reduced by about one-third (hazard ratio, 0.67; P = .0165).
On a patient level, a 0.1-unit increase in lowest post-PCI FFR of any assessed vessel was also associated with the same relative risk reduction (HR, 0.65; P = .0074) in the outcomes of cardiac death, target vessel MI, or target vessel revascularization, according to Dr. Piroth. On a receiver operating characteristic curve analysis, a value of 0.88 or below was predictive of TVF.
Although several other patient characteristics were also risk predictors of TVF on univariate analysis, only renal disease and the single lowest post-PCI FFR (as a continuous variable) emerged as predictors of TVF on multivariable analysis after adjustment for key clinical parameters, Dr. Piroth reported.
The reason why post-PCI FFR was not performed in almost 40% of patients randomized to PCI is unclear, but Dr. Piroth reported that the baseline characteristics of those who were or were not assessed with FFR after their procedure did not differ to any major degree.
Despite “a trend for improved outcomes in those who underwent post-PCI FFR,” Dr. Piroth, whose substudy was published in Circulation: Cardiovascular Interventions simultaneously with his TCT presentation, acknowledged that the reasons for a potential benefit cannot be derived from this post hoc analysis.
As for the prognostic value of IVUS, any conclusions are limited by the small proportion of patients who underwent this form of imaging. Overall, IVUS imaging was associated with longer procedures and more stents and “if anything, a signal for harm” in this analysis, but Dr. Piroth cautioned against any conclusions because of the small data pool.
The prognostic value of post-PCI FFR in complex multivessel disease is supported by these data, but the analysis was not designed to determine whether post-PCI FFR has relevance to intervention.
According to J. Dawn Abbott, MD, an FFR analysis conducted to identify lesions that are candidates for treatment should not be confused with FFR for physiologically guided PCI to optimize outcomes.
Noting that post-PCI FFR was encouraged in this study but not mandated and that these FFR values did not typically or necessarily lead to a change in management, take home messages about the value of post-PCI FFR in multivessel disease remain limited, said Dr. Abbott, director of interventional cardiology fellowship training, Brown University, Providence, R.I.
“There was a trend toward improved outcomes in patients who had this measurement done, but, unfortunately, we do not have data regarding whether these patients had further interventions performed,” Dr. Piroth acknowledged.
The post-PCI FFR values were made available to the treating physicians, but Dr. Piroth reiterated that it is unknown whether the physicians considered this information actionable. Moreover, “the vast majority had a nonsignificant post-PCI FFR” result, and “all of the patients had an angiographically successful PCI,” Dr. Piroth added.
Dr. Piroth has financial relationships with Abbott Vascular and Boston Scientific. Dr. Abbott reports financial relationships with Abbott Vascular, Boston Scientific, Medtronic, Microport, Philips, Penumbra, Recor, and Shockwave.
FROM TCT 2022
Night owls may have greater risks of T2D and CVD
In the study involving 51 people, night owls metabolized fat less efficiently, showed less insulin sensitivity, and demonstrated lower physical fitness than early birds, lead author Steven K. Malin, PhD, of Rutgers University, New Brunswick, N.J., and colleagues reported.
Prior publications have suggested that night owls, formally known as “late chronotypes,” have an increased risk of obesity, type 2 diabetes, and cardiovascular disease, Dr. Malin said in an interview. But no previous research involved the gold-standard measurement tools used in this study, including euglycemic clamp and indirect calorimetry to quantify fat metabolism.
Dr. Malin also noted that this is the first study of its kind to characterize metabolism during both rest and exercise.
The study, published in Experimental Physiology, involved 24 early birds and 27 night owls classified by the Morning-Eveningness Questionnaire. All participants were sedentary, reporting less than one hour of structured exercise per week, and had metabolic syndrome according to Adult Treatment Panel III report criteria. Groups were otherwise demographically similar, with average ages in each group of approximately 54-55 years.
Compared with night owls, early birds were more physically active during the morning into midday. During exercise, they metabolized more fat and demonstrated greater physical fitness based on VO2max readings. At rest, early birds also came out ahead – they had higher fat oxidation and non–oxidative glucose disposal, suggesting more sensitivity to insulin.
“Collectively, this work highlights and supports chronotype as a potential risk factor related to type 2 diabetes and cardiovascular disease risk,” the investigators concluded.
Night owls have less metabolic control
Jed Friedman, PhD, director of OU Health Harold Hamm Diabetes Center at the University of Oklahoma Health Sciences Center, Oklahoma City, praised the study for the size of the groups the researchers compared with each other and how well matched those groups were, as well as the “state-of-the-art” measurement tools employed.
The findings show that night owls have “less metabolic control,” Dr. Friedman said in an interview.
“That’s a term that’s frequently invoked in [regard to] prediabetes,” he said. “Blood sugar goes up, because when you’re eating a high carbohydrate diet, your cells aren’t metabolizing sugar properly. That tends to raise your risk for a lot of diseases.”
Dr. Friedman added that the findings align with those of previous studies that have linked less sleep with changes in brain biology, and therefore behavior, especially in dietary choices.
“When you’re tired, the mechanisms for appetite control go haywire,” Dr. Friedman explained. “The evidence suggests that sugar is the primary driver for what people eat when they’re tired. That obviously has implications for diabetes and metabolic syndrome. So sleeping more really can help you control cravings.”
Dr. Friedman also noted that people who are tired tend to engage in less physical activity, further increasing their risk of metabolic issues. To control this risk, he advised people to return to their circadian rhythms, which could mean forgetting the midnight snack.
“Having a daily pattern that’s in sync with chronicity, or these daily rhythms, is associated with greater health,” Dr. Friedman said. “We’re not really made to eat at night. I think this [study] kind of reinforces that.”
Can a night owl become an early bird?
When asked if a person’s natural circadian rhythm can be later, Dr. Malin responded that chronotypes may be dictated by genetics and age, as well as external drivers like work schedule. For these reasons, it’s “tricky” to answer whether night owls can turn into early birds and reap the potential health benefits of making that shift.
“Given that so many life factors can influence what our routine entails, it’s hard to know if we [can] truly change our chronotype or if rather we [can] learn to manage,” Dr. Malin said. “In either case, there is some work that suggests people can adopt earlier bedtimes and waketimes through practical recommendations.”
Specifically, he suggested increasing physical activity during the day, and adjusting bedtimes gradually by 15-minute increments.
“Go to bed 15 minutes earlier then wake up 15 minutes earlier,” Dr. Malin said. “In time, and depending on how things are going, this can expand to another 15-minute window. Then, during the earlier time waking up, a person can engage in light physical activity to help with promoting general fitness. If they can get outside with sunlight, that would be great too, as the natural sunlight would provide cues to the circadian system to adjust.”
The study was supported by the National Institutes of Health. The investigators and Dr. Friedman disclosed no conflicts of interest.
In the study involving 51 people, night owls metabolized fat less efficiently, showed less insulin sensitivity, and demonstrated lower physical fitness than early birds, lead author Steven K. Malin, PhD, of Rutgers University, New Brunswick, N.J., and colleagues reported.
Prior publications have suggested that night owls, formally known as “late chronotypes,” have an increased risk of obesity, type 2 diabetes, and cardiovascular disease, Dr. Malin said in an interview. But no previous research involved the gold-standard measurement tools used in this study, including euglycemic clamp and indirect calorimetry to quantify fat metabolism.
Dr. Malin also noted that this is the first study of its kind to characterize metabolism during both rest and exercise.
The study, published in Experimental Physiology, involved 24 early birds and 27 night owls classified by the Morning-Eveningness Questionnaire. All participants were sedentary, reporting less than one hour of structured exercise per week, and had metabolic syndrome according to Adult Treatment Panel III report criteria. Groups were otherwise demographically similar, with average ages in each group of approximately 54-55 years.
Compared with night owls, early birds were more physically active during the morning into midday. During exercise, they metabolized more fat and demonstrated greater physical fitness based on VO2max readings. At rest, early birds also came out ahead – they had higher fat oxidation and non–oxidative glucose disposal, suggesting more sensitivity to insulin.
“Collectively, this work highlights and supports chronotype as a potential risk factor related to type 2 diabetes and cardiovascular disease risk,” the investigators concluded.
Night owls have less metabolic control
Jed Friedman, PhD, director of OU Health Harold Hamm Diabetes Center at the University of Oklahoma Health Sciences Center, Oklahoma City, praised the study for the size of the groups the researchers compared with each other and how well matched those groups were, as well as the “state-of-the-art” measurement tools employed.
The findings show that night owls have “less metabolic control,” Dr. Friedman said in an interview.
“That’s a term that’s frequently invoked in [regard to] prediabetes,” he said. “Blood sugar goes up, because when you’re eating a high carbohydrate diet, your cells aren’t metabolizing sugar properly. That tends to raise your risk for a lot of diseases.”
Dr. Friedman added that the findings align with those of previous studies that have linked less sleep with changes in brain biology, and therefore behavior, especially in dietary choices.
“When you’re tired, the mechanisms for appetite control go haywire,” Dr. Friedman explained. “The evidence suggests that sugar is the primary driver for what people eat when they’re tired. That obviously has implications for diabetes and metabolic syndrome. So sleeping more really can help you control cravings.”
Dr. Friedman also noted that people who are tired tend to engage in less physical activity, further increasing their risk of metabolic issues. To control this risk, he advised people to return to their circadian rhythms, which could mean forgetting the midnight snack.
“Having a daily pattern that’s in sync with chronicity, or these daily rhythms, is associated with greater health,” Dr. Friedman said. “We’re not really made to eat at night. I think this [study] kind of reinforces that.”
Can a night owl become an early bird?
When asked if a person’s natural circadian rhythm can be later, Dr. Malin responded that chronotypes may be dictated by genetics and age, as well as external drivers like work schedule. For these reasons, it’s “tricky” to answer whether night owls can turn into early birds and reap the potential health benefits of making that shift.
“Given that so many life factors can influence what our routine entails, it’s hard to know if we [can] truly change our chronotype or if rather we [can] learn to manage,” Dr. Malin said. “In either case, there is some work that suggests people can adopt earlier bedtimes and waketimes through practical recommendations.”
Specifically, he suggested increasing physical activity during the day, and adjusting bedtimes gradually by 15-minute increments.
“Go to bed 15 minutes earlier then wake up 15 minutes earlier,” Dr. Malin said. “In time, and depending on how things are going, this can expand to another 15-minute window. Then, during the earlier time waking up, a person can engage in light physical activity to help with promoting general fitness. If they can get outside with sunlight, that would be great too, as the natural sunlight would provide cues to the circadian system to adjust.”
The study was supported by the National Institutes of Health. The investigators and Dr. Friedman disclosed no conflicts of interest.
In the study involving 51 people, night owls metabolized fat less efficiently, showed less insulin sensitivity, and demonstrated lower physical fitness than early birds, lead author Steven K. Malin, PhD, of Rutgers University, New Brunswick, N.J., and colleagues reported.
Prior publications have suggested that night owls, formally known as “late chronotypes,” have an increased risk of obesity, type 2 diabetes, and cardiovascular disease, Dr. Malin said in an interview. But no previous research involved the gold-standard measurement tools used in this study, including euglycemic clamp and indirect calorimetry to quantify fat metabolism.
Dr. Malin also noted that this is the first study of its kind to characterize metabolism during both rest and exercise.
The study, published in Experimental Physiology, involved 24 early birds and 27 night owls classified by the Morning-Eveningness Questionnaire. All participants were sedentary, reporting less than one hour of structured exercise per week, and had metabolic syndrome according to Adult Treatment Panel III report criteria. Groups were otherwise demographically similar, with average ages in each group of approximately 54-55 years.
Compared with night owls, early birds were more physically active during the morning into midday. During exercise, they metabolized more fat and demonstrated greater physical fitness based on VO2max readings. At rest, early birds also came out ahead – they had higher fat oxidation and non–oxidative glucose disposal, suggesting more sensitivity to insulin.
“Collectively, this work highlights and supports chronotype as a potential risk factor related to type 2 diabetes and cardiovascular disease risk,” the investigators concluded.
Night owls have less metabolic control
Jed Friedman, PhD, director of OU Health Harold Hamm Diabetes Center at the University of Oklahoma Health Sciences Center, Oklahoma City, praised the study for the size of the groups the researchers compared with each other and how well matched those groups were, as well as the “state-of-the-art” measurement tools employed.
The findings show that night owls have “less metabolic control,” Dr. Friedman said in an interview.
“That’s a term that’s frequently invoked in [regard to] prediabetes,” he said. “Blood sugar goes up, because when you’re eating a high carbohydrate diet, your cells aren’t metabolizing sugar properly. That tends to raise your risk for a lot of diseases.”
Dr. Friedman added that the findings align with those of previous studies that have linked less sleep with changes in brain biology, and therefore behavior, especially in dietary choices.
“When you’re tired, the mechanisms for appetite control go haywire,” Dr. Friedman explained. “The evidence suggests that sugar is the primary driver for what people eat when they’re tired. That obviously has implications for diabetes and metabolic syndrome. So sleeping more really can help you control cravings.”
Dr. Friedman also noted that people who are tired tend to engage in less physical activity, further increasing their risk of metabolic issues. To control this risk, he advised people to return to their circadian rhythms, which could mean forgetting the midnight snack.
“Having a daily pattern that’s in sync with chronicity, or these daily rhythms, is associated with greater health,” Dr. Friedman said. “We’re not really made to eat at night. I think this [study] kind of reinforces that.”
Can a night owl become an early bird?
When asked if a person’s natural circadian rhythm can be later, Dr. Malin responded that chronotypes may be dictated by genetics and age, as well as external drivers like work schedule. For these reasons, it’s “tricky” to answer whether night owls can turn into early birds and reap the potential health benefits of making that shift.
“Given that so many life factors can influence what our routine entails, it’s hard to know if we [can] truly change our chronotype or if rather we [can] learn to manage,” Dr. Malin said. “In either case, there is some work that suggests people can adopt earlier bedtimes and waketimes through practical recommendations.”
Specifically, he suggested increasing physical activity during the day, and adjusting bedtimes gradually by 15-minute increments.
“Go to bed 15 minutes earlier then wake up 15 minutes earlier,” Dr. Malin said. “In time, and depending on how things are going, this can expand to another 15-minute window. Then, during the earlier time waking up, a person can engage in light physical activity to help with promoting general fitness. If they can get outside with sunlight, that would be great too, as the natural sunlight would provide cues to the circadian system to adjust.”
The study was supported by the National Institutes of Health. The investigators and Dr. Friedman disclosed no conflicts of interest.
FROM EXPERIMENTAL PHYSIOLOGY
Angiography in patients with prior CABG does better when planned with CT
BOSTON – Coronary angiography in patients who have previously undergone cardiac artery bypass grafting (CABG) is challenging, but the procedure can be streamlined and made safer when preprocedural CT coronary angiography (CTCA) is performed to plan the intervention, according to a randomized controlled trial.
In this study, all three endpoints, including a reduction in the incidence of contrast-induced nephropathy (CIN) and duration of the procedure, were met, according to Daniel Jones, MBBS, PhD.
Preprocedural CTCA was also associated with about a 40% improvement in patient satisfaction.
“When logistically possible, CTCA should be considered for any stable postbypass patient undergoing coronary angiography,” said Dr. Jones, who supported this assertion with data presented at the Transcatheter Cardiovascular Therapeutics annual meeting.
In this study, called BYPASS-CTCA, 688 patients with a prior CABG scheduled for invasive coronary angiography were randomized to a preprocedural CTCA or no preprocedural CTCA. Patients with stable angina and those with a non–ST elevated acute coronary syndrome were eligible. Those with ST-segment elevated MI or severe renal impairment (eGFR < 20 mL/min) were excluded.
All three co–primary endpoints favor CTCA
CTCA relative to no CTCA provided a significant advantage for all three of the coprimary endpoints, which were procedure duration, CIN as defined by KDIGO criteria, and patient satisfaction as measured by questionnaire.
The procedure duration was reduced by almost 21 minutes, cutting the time from nearly 39 minutes to less than 18 minutes (P < .001). This relative reduction was of similar magnitude across groups, such as those with or without acute coronary syndrome and procedures performed by a senior or a junior operator.
“Even when you include the preprocedural CTCA evaluation time, there was still a significant reduction [P < .001] in duration for those in the CTCA arm,” reported Dr. Jones, honorary consultant cardiologist, Barts Heart Centre, Queen Mary University, London.
The rates of CIN following the procedure in this study, which had a follow-up of 12 months, were 3.4% versus 27.9% (P < .0001) in the preprocedural CTCA and non-CTCA groups, respectively. Again, a sensitivity analysis showed a similar magnitude of risk reduction across all subgroups evaluated.
CTCA planning reduced contrast exposure
The reduced risk of CIN was consistent with a large reduction in contrast exposure for those in the CTCA group (77.4 vs. 173.0 mL; P < .001). The advantage narrowed substantially when adding in contrast exposure from CTCA, but still remained statistically significant (148.9 vs. 173.0 mL; P < .001).
Dr. Jones did not speculate about the specific reasons for the 40% improvement in patient satisfaction among those who underwent preprocedural CTCA relative to those who did not, but, again, a sensitivity analysis showed consistency across subgroups defined by race, operator experience, and underlying diagnosis.
Numerous secondary endpoints also favored CTCA over no CTCA. This included fewer catheters used to complete the procedure (three vs. four; P < .001), a greater likelihood that the procedure was performed with radial access (76.9% vs. 56.7%), and lower rates of procedural complications (2.3% vs. 10.8%; P < .001). This latter category included fewer vascular access complications such as bleeding (0.6 % vs. 4.4%; P = .007) and periprocedural MI (0.6% vs. 6.4%; P < 0.001).
In a graph of time to first major adverse cardiovascular event (MACE), the curves separated almost immediately with a consistently lower rate maintained in the CTCA arm over the 12 months of follow-up, but this is observational. Dr. Jones acknowledged that this trial was not powered to show a difference in MACE.
Study intriguing but not definitive
In a panel discussion that followed the presentation of these results at the meeting, sponsored by the Cardiovascular Research Foundation, some reservations with this study were expressed. In particular, several of the panelists, including Jeffrey W. Moses, MD, director of interventional cardiovascular therapeutics, Columbia University Medical Center, New York, expressed surprise at the 27% rate of CIN, which he considered uncommonly high even in a high-risk population.
The unusual rate of CIN was also considered problematic given that it was the most significant clinical outcome among the three co–primary endpoints. Procedural times and patient satisfaction, while valid endpoints, are important subjects of study, but Dr. Moses was not alone in suggesting this study deserves validation.
In particular, there appeared to be a consensus among panelists that a larger multicenter study looking at hard endpoints, such as MACE, would be more compelling. They indicated that even if CTCA poses a very low risk of meaningful complications, it does add expense and an extra step.
Dr. Jones reported no potential conflicts of interest. Dr. Moses reported financial relationships with Covanos, Orchestra Biomed, Ostial, and Xenter.
BOSTON – Coronary angiography in patients who have previously undergone cardiac artery bypass grafting (CABG) is challenging, but the procedure can be streamlined and made safer when preprocedural CT coronary angiography (CTCA) is performed to plan the intervention, according to a randomized controlled trial.
In this study, all three endpoints, including a reduction in the incidence of contrast-induced nephropathy (CIN) and duration of the procedure, were met, according to Daniel Jones, MBBS, PhD.
Preprocedural CTCA was also associated with about a 40% improvement in patient satisfaction.
“When logistically possible, CTCA should be considered for any stable postbypass patient undergoing coronary angiography,” said Dr. Jones, who supported this assertion with data presented at the Transcatheter Cardiovascular Therapeutics annual meeting.
In this study, called BYPASS-CTCA, 688 patients with a prior CABG scheduled for invasive coronary angiography were randomized to a preprocedural CTCA or no preprocedural CTCA. Patients with stable angina and those with a non–ST elevated acute coronary syndrome were eligible. Those with ST-segment elevated MI or severe renal impairment (eGFR < 20 mL/min) were excluded.
All three co–primary endpoints favor CTCA
CTCA relative to no CTCA provided a significant advantage for all three of the coprimary endpoints, which were procedure duration, CIN as defined by KDIGO criteria, and patient satisfaction as measured by questionnaire.
The procedure duration was reduced by almost 21 minutes, cutting the time from nearly 39 minutes to less than 18 minutes (P < .001). This relative reduction was of similar magnitude across groups, such as those with or without acute coronary syndrome and procedures performed by a senior or a junior operator.
“Even when you include the preprocedural CTCA evaluation time, there was still a significant reduction [P < .001] in duration for those in the CTCA arm,” reported Dr. Jones, honorary consultant cardiologist, Barts Heart Centre, Queen Mary University, London.
The rates of CIN following the procedure in this study, which had a follow-up of 12 months, were 3.4% versus 27.9% (P < .0001) in the preprocedural CTCA and non-CTCA groups, respectively. Again, a sensitivity analysis showed a similar magnitude of risk reduction across all subgroups evaluated.
CTCA planning reduced contrast exposure
The reduced risk of CIN was consistent with a large reduction in contrast exposure for those in the CTCA group (77.4 vs. 173.0 mL; P < .001). The advantage narrowed substantially when adding in contrast exposure from CTCA, but still remained statistically significant (148.9 vs. 173.0 mL; P < .001).
Dr. Jones did not speculate about the specific reasons for the 40% improvement in patient satisfaction among those who underwent preprocedural CTCA relative to those who did not, but, again, a sensitivity analysis showed consistency across subgroups defined by race, operator experience, and underlying diagnosis.
Numerous secondary endpoints also favored CTCA over no CTCA. This included fewer catheters used to complete the procedure (three vs. four; P < .001), a greater likelihood that the procedure was performed with radial access (76.9% vs. 56.7%), and lower rates of procedural complications (2.3% vs. 10.8%; P < .001). This latter category included fewer vascular access complications such as bleeding (0.6 % vs. 4.4%; P = .007) and periprocedural MI (0.6% vs. 6.4%; P < 0.001).
In a graph of time to first major adverse cardiovascular event (MACE), the curves separated almost immediately with a consistently lower rate maintained in the CTCA arm over the 12 months of follow-up, but this is observational. Dr. Jones acknowledged that this trial was not powered to show a difference in MACE.
Study intriguing but not definitive
In a panel discussion that followed the presentation of these results at the meeting, sponsored by the Cardiovascular Research Foundation, some reservations with this study were expressed. In particular, several of the panelists, including Jeffrey W. Moses, MD, director of interventional cardiovascular therapeutics, Columbia University Medical Center, New York, expressed surprise at the 27% rate of CIN, which he considered uncommonly high even in a high-risk population.
The unusual rate of CIN was also considered problematic given that it was the most significant clinical outcome among the three co–primary endpoints. Procedural times and patient satisfaction, while valid endpoints, are important subjects of study, but Dr. Moses was not alone in suggesting this study deserves validation.
In particular, there appeared to be a consensus among panelists that a larger multicenter study looking at hard endpoints, such as MACE, would be more compelling. They indicated that even if CTCA poses a very low risk of meaningful complications, it does add expense and an extra step.
Dr. Jones reported no potential conflicts of interest. Dr. Moses reported financial relationships with Covanos, Orchestra Biomed, Ostial, and Xenter.
BOSTON – Coronary angiography in patients who have previously undergone cardiac artery bypass grafting (CABG) is challenging, but the procedure can be streamlined and made safer when preprocedural CT coronary angiography (CTCA) is performed to plan the intervention, according to a randomized controlled trial.
In this study, all three endpoints, including a reduction in the incidence of contrast-induced nephropathy (CIN) and duration of the procedure, were met, according to Daniel Jones, MBBS, PhD.
Preprocedural CTCA was also associated with about a 40% improvement in patient satisfaction.
“When logistically possible, CTCA should be considered for any stable postbypass patient undergoing coronary angiography,” said Dr. Jones, who supported this assertion with data presented at the Transcatheter Cardiovascular Therapeutics annual meeting.
In this study, called BYPASS-CTCA, 688 patients with a prior CABG scheduled for invasive coronary angiography were randomized to a preprocedural CTCA or no preprocedural CTCA. Patients with stable angina and those with a non–ST elevated acute coronary syndrome were eligible. Those with ST-segment elevated MI or severe renal impairment (eGFR < 20 mL/min) were excluded.
All three co–primary endpoints favor CTCA
CTCA relative to no CTCA provided a significant advantage for all three of the coprimary endpoints, which were procedure duration, CIN as defined by KDIGO criteria, and patient satisfaction as measured by questionnaire.
The procedure duration was reduced by almost 21 minutes, cutting the time from nearly 39 minutes to less than 18 minutes (P < .001). This relative reduction was of similar magnitude across groups, such as those with or without acute coronary syndrome and procedures performed by a senior or a junior operator.
“Even when you include the preprocedural CTCA evaluation time, there was still a significant reduction [P < .001] in duration for those in the CTCA arm,” reported Dr. Jones, honorary consultant cardiologist, Barts Heart Centre, Queen Mary University, London.
The rates of CIN following the procedure in this study, which had a follow-up of 12 months, were 3.4% versus 27.9% (P < .0001) in the preprocedural CTCA and non-CTCA groups, respectively. Again, a sensitivity analysis showed a similar magnitude of risk reduction across all subgroups evaluated.
CTCA planning reduced contrast exposure
The reduced risk of CIN was consistent with a large reduction in contrast exposure for those in the CTCA group (77.4 vs. 173.0 mL; P < .001). The advantage narrowed substantially when adding in contrast exposure from CTCA, but still remained statistically significant (148.9 vs. 173.0 mL; P < .001).
Dr. Jones did not speculate about the specific reasons for the 40% improvement in patient satisfaction among those who underwent preprocedural CTCA relative to those who did not, but, again, a sensitivity analysis showed consistency across subgroups defined by race, operator experience, and underlying diagnosis.
Numerous secondary endpoints also favored CTCA over no CTCA. This included fewer catheters used to complete the procedure (three vs. four; P < .001), a greater likelihood that the procedure was performed with radial access (76.9% vs. 56.7%), and lower rates of procedural complications (2.3% vs. 10.8%; P < .001). This latter category included fewer vascular access complications such as bleeding (0.6 % vs. 4.4%; P = .007) and periprocedural MI (0.6% vs. 6.4%; P < 0.001).
In a graph of time to first major adverse cardiovascular event (MACE), the curves separated almost immediately with a consistently lower rate maintained in the CTCA arm over the 12 months of follow-up, but this is observational. Dr. Jones acknowledged that this trial was not powered to show a difference in MACE.
Study intriguing but not definitive
In a panel discussion that followed the presentation of these results at the meeting, sponsored by the Cardiovascular Research Foundation, some reservations with this study were expressed. In particular, several of the panelists, including Jeffrey W. Moses, MD, director of interventional cardiovascular therapeutics, Columbia University Medical Center, New York, expressed surprise at the 27% rate of CIN, which he considered uncommonly high even in a high-risk population.
The unusual rate of CIN was also considered problematic given that it was the most significant clinical outcome among the three co–primary endpoints. Procedural times and patient satisfaction, while valid endpoints, are important subjects of study, but Dr. Moses was not alone in suggesting this study deserves validation.
In particular, there appeared to be a consensus among panelists that a larger multicenter study looking at hard endpoints, such as MACE, would be more compelling. They indicated that even if CTCA poses a very low risk of meaningful complications, it does add expense and an extra step.
Dr. Jones reported no potential conflicts of interest. Dr. Moses reported financial relationships with Covanos, Orchestra Biomed, Ostial, and Xenter.
AT TCT 2022