ACC 2017

A new study suggests calcium scores may help physicians as they navigate a wide cardiac screening guideline gap over recommendations about statin therapy in African Americans.

In a study sample of Mississippi residents, researchers found that the 2016 U.S. Preventive Services Task Force guidelines would reject statins for a quarter of the African Americans who’d be deemed statin eligible by the 2013 American College of Cardiology/American Heart Association (ACC/AHA) recommendations.

“ACC/AHA guidelines are more sensitive, but may lead to overtreatment of those who may not be at increased risk of cardiovascular disease,” said study coauthor Aferdita Spahillari, MD, a cardiology fellow at Tufts Medical Center and Beth Israel Deaconess Medical Center, Boston. In contrast, the task force guidelines “are more specific, yet they may miss individuals at higher risk who should be treated with statins,” she said.

Regardless of which screening guidelines are used, Dr. Spahillari said, “calcium scoring may aid decision making in those cases where guideline recommendations may be divergent.”

The study was presented at the annual meeting of the American College of Cardiology and published simultaneously in the JAMA Cardiology (doi: 10.1001/jamacardio.2017.0944).

The researchers sought to answer these questions: How do the ACC/AHA and task force guidelines perform at identifying at-risk African Americans? And can calcium scores help refine decisions regarding statins? According to Dr. Spahillari, the latter issue has been studied in whites but not large African American populations.

Insight could help physicians better provide preventive treatment to African Americans, who face a higher risk of cardiac problems compared with whites. In addition, “studies have shown that racial disparities exist in prescription of cardioprotective medications,” Dr. Spahillari said, “and African Americans are prescribed statins less frequently than whites.”

For the new study, researchers tracked 2,812 African American individuals aged 40-75 years (mean age 55 [SD 9.4], 65.3% female, mean body mass index 31.6 kg/m² [SD 7.0]) in the Jackson, Miss., area. They were examined in 2000-2004, 2005-2008, and 2009-2013 and included if they didn’t show signs of prevalent subclinical and clinical atherosclerotic cardiovascular disease and weren’t on statins at baseline.

If the task force guidelines regarding 10-year risk had been in existence, 1,072 (38.1%) of the participants would have been deemed eligible for treatment. A higher number – 1,404 (49.9%) – would have been eligible under ACC/AHA guidelines (risk difference, 11.8%; 95% CI, 10.5-13.1; P less than .001).

The two sets of guidelines diverged on the eligibility of 13.8% of the total subjects: 361 (12.8%) were deemed eligible for statins by the ACC/AHA guidelines alone. (They account for 25.7% of all the statin-eligible subjects under the ACC/AHA guidelines.)

In contrast, the task force guidelines alone deemed 29 (1%) to be eligible.

Those deemed eligible for statins under both guidelines had a cardiovascular event rate of 9.6 per 1,000 patient-years (95% CI, 7.8-11.8, P = .003) over a median 10-year follow-up. The event rate for those only statin-eligible under the ACC/AHA guidelines had an event rate of 4.1 events per 1,000 patient-years (95% CI, 2.4-6.9; P = .003), which Dr. Spahillari calls “a low to intermediate rate suggesting a decreased sensitivity of the task force recommendations in identifying participants at risk of atherosclerotic cardiovascular disease.”

And what about CAC levels? Task force guidelines identified 404 of 732 (55.2%) African Americans with coronary calcium; ACC/AHA guidelines identified 507 (69.3%).

“Participants eligible for statins under the ACC/AHA guidelines who had CAC were at higher risk than those without CAC,” Dr. Spahillari said. Specifically, among those deemed eligible for statins by the ACC/AHA recommendations, the 10-year event rate per 1,000 person-years was 8.1 (95% CI, 5.9-11.1) in those with CAC and 3.1 (95% CI, 1.6-5.9) in those without CAC (P = .02).

The situation was different under the task force guidelines. CAC didn’t significantly affect the risk in those deemed eligible for statins by the task force guidelines, but it did seem to boost risk in those who weren’t statin eligible, she said.

Among those deemed not statin eligible by the task force guidelines, the event rate per 1,000 person-years was 2.8 in those with CAC (95% CI, 1.5-5.4) and 0.8 in those without (95%, CI 0.3-1.7) (P = .03).

How could CAC levels be useful for physicians? “As the role of CAC measurement is evolving, our findings support that measurement of CAC in an African-American population with an intermediate risk score would be clinically useful,” Dr. Spahillari said.

When ACC/AHA guidelines are used, she said, “the absence of CAC may reduce the number of individuals indicated for treatment with statins by ACC/AHA recommendations and temper concerns for overtreatment.”

What if a physician uses the task force guidelines in this population? “The presence of CAC may push a recommendation for statin treatment in individuals who would otherwise not be indicated for statins,” she said.

The National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities funded the study. One author reported funding from a National Institutes of Health grant. The others had no disclosures.

A new study suggests calcium scores may help physicians as they navigate a wide cardiac screening guideline gap over recommendations about statin therapy in African Americans.

In a study sample of Mississippi residents, researchers found that the 2016 U.S. Preventive Services Task Force guidelines would reject statins for a quarter of the African Americans who’d be deemed statin eligible by the 2013 American College of Cardiology/American Heart Association (ACC/AHA) recommendations.

“ACC/AHA guidelines are more sensitive, but may lead to overtreatment of those who may not be at increased risk of cardiovascular disease,” said study coauthor Aferdita Spahillari, MD, a cardiology fellow at Tufts Medical Center and Beth Israel Deaconess Medical Center, Boston. In contrast, the task force guidelines “are more specific, yet they may miss individuals at higher risk who should be treated with statins,” she said.

Regardless of which screening guidelines are used, Dr. Spahillari said, “calcium scoring may aid decision making in those cases where guideline recommendations may be divergent.”

The study was presented at the annual meeting of the American College of Cardiology and published simultaneously in the JAMA Cardiology (doi: 10.1001/jamacardio.2017.0944).

The researchers sought to answer these questions: How do the ACC/AHA and task force guidelines perform at identifying at-risk African Americans? And can calcium scores help refine decisions regarding statins? According to Dr. Spahillari, the latter issue has been studied in whites but not large African American populations.

Insight could help physicians better provide preventive treatment to African Americans, who face a higher risk of cardiac problems compared with whites. In addition, “studies have shown that racial disparities exist in prescription of cardioprotective medications,” Dr. Spahillari said, “and African Americans are prescribed statins less frequently than whites.”

For the new study, researchers tracked 2,812 African American individuals aged 40-75 years (mean age 55 [SD 9.4], 65.3% female, mean body mass index 31.6 kg/m² [SD 7.0]) in the Jackson, Miss., area. They were examined in 2000-2004, 2005-2008, and 2009-2013 and included if they didn’t show signs of prevalent subclinical and clinical atherosclerotic cardiovascular disease and weren’t on statins at baseline.

If the task force guidelines regarding 10-year risk had been in existence, 1,072 (38.1%) of the participants would have been deemed eligible for treatment. A higher number – 1,404 (49.9%) – would have been eligible under ACC/AHA guidelines (risk difference, 11.8%; 95% CI, 10.5-13.1; P less than .001).

The two sets of guidelines diverged on the eligibility of 13.8% of the total subjects: 361 (12.8%) were deemed eligible for statins by the ACC/AHA guidelines alone. (They account for 25.7% of all the statin-eligible subjects under the ACC/AHA guidelines.)

In contrast, the task force guidelines alone deemed 29 (1%) to be eligible.

Those deemed eligible for statins under both guidelines had a cardiovascular event rate of 9.6 per 1,000 patient-years (95% CI, 7.8-11.8, P = .003) over a median 10-year follow-up. The event rate for those only statin-eligible under the ACC/AHA guidelines had an event rate of 4.1 events per 1,000 patient-years (95% CI, 2.4-6.9; P = .003), which Dr. Spahillari calls “a low to intermediate rate suggesting a decreased sensitivity of the task force recommendations in identifying participants at risk of atherosclerotic cardiovascular disease.”

And what about CAC levels? Task force guidelines identified 404 of 732 (55.2%) African Americans with coronary calcium; ACC/AHA guidelines identified 507 (69.3%).

“Participants eligible for statins under the ACC/AHA guidelines who had CAC were at higher risk than those without CAC,” Dr. Spahillari said. Specifically, among those deemed eligible for statins by the ACC/AHA recommendations, the 10-year event rate per 1,000 person-years was 8.1 (95% CI, 5.9-11.1) in those with CAC and 3.1 (95% CI, 1.6-5.9) in those without CAC (P = .02).

The situation was different under the task force guidelines. CAC didn’t significantly affect the risk in those deemed eligible for statins by the task force guidelines, but it did seem to boost risk in those who weren’t statin eligible, she said.

Among those deemed not statin eligible by the task force guidelines, the event rate per 1,000 person-years was 2.8 in those with CAC (95% CI, 1.5-5.4) and 0.8 in those without (95%, CI 0.3-1.7) (P = .03).

How could CAC levels be useful for physicians? “As the role of CAC measurement is evolving, our findings support that measurement of CAC in an African-American population with an intermediate risk score would be clinically useful,” Dr. Spahillari said.

When ACC/AHA guidelines are used, she said, “the absence of CAC may reduce the number of individuals indicated for treatment with statins by ACC/AHA recommendations and temper concerns for overtreatment.”

What if a physician uses the task force guidelines in this population? “The presence of CAC may push a recommendation for statin treatment in individuals who would otherwise not be indicated for statins,” she said.

The National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities funded the study. One author reported funding from a National Institutes of Health grant. The others had no disclosures.

A new study suggests calcium scores may help physicians as they navigate a wide cardiac screening guideline gap over recommendations about statin therapy in African Americans.

In a study sample of Mississippi residents, researchers found that the 2016 U.S. Preventive Services Task Force guidelines would reject statins for a quarter of the African Americans who’d be deemed statin eligible by the 2013 American College of Cardiology/American Heart Association (ACC/AHA) recommendations.

“ACC/AHA guidelines are more sensitive, but may lead to overtreatment of those who may not be at increased risk of cardiovascular disease,” said study coauthor Aferdita Spahillari, MD, a cardiology fellow at Tufts Medical Center and Beth Israel Deaconess Medical Center, Boston. In contrast, the task force guidelines “are more specific, yet they may miss individuals at higher risk who should be treated with statins,” she said.

Regardless of which screening guidelines are used, Dr. Spahillari said, “calcium scoring may aid decision making in those cases where guideline recommendations may be divergent.”

The study was presented at the annual meeting of the American College of Cardiology and published simultaneously in the JAMA Cardiology (doi: 10.1001/jamacardio.2017.0944).

The researchers sought to answer these questions: How do the ACC/AHA and task force guidelines perform at identifying at-risk African Americans? And can calcium scores help refine decisions regarding statins? According to Dr. Spahillari, the latter issue has been studied in whites but not large African American populations.

Insight could help physicians better provide preventive treatment to African Americans, who face a higher risk of cardiac problems compared with whites. In addition, “studies have shown that racial disparities exist in prescription of cardioprotective medications,” Dr. Spahillari said, “and African Americans are prescribed statins less frequently than whites.”

For the new study, researchers tracked 2,812 African American individuals aged 40-75 years (mean age 55 [SD 9.4], 65.3% female, mean body mass index 31.6 kg/m² [SD 7.0]) in the Jackson, Miss., area. They were examined in 2000-2004, 2005-2008, and 2009-2013 and included if they didn’t show signs of prevalent subclinical and clinical atherosclerotic cardiovascular disease and weren’t on statins at baseline.

If the task force guidelines regarding 10-year risk had been in existence, 1,072 (38.1%) of the participants would have been deemed eligible for treatment. A higher number – 1,404 (49.9%) – would have been eligible under ACC/AHA guidelines (risk difference, 11.8%; 95% CI, 10.5-13.1; P less than .001).

The two sets of guidelines diverged on the eligibility of 13.8% of the total subjects: 361 (12.8%) were deemed eligible for statins by the ACC/AHA guidelines alone. (They account for 25.7% of all the statin-eligible subjects under the ACC/AHA guidelines.)

In contrast, the task force guidelines alone deemed 29 (1%) to be eligible.

Those deemed eligible for statins under both guidelines had a cardiovascular event rate of 9.6 per 1,000 patient-years (95% CI, 7.8-11.8, P = .003) over a median 10-year follow-up. The event rate for those only statin-eligible under the ACC/AHA guidelines had an event rate of 4.1 events per 1,000 patient-years (95% CI, 2.4-6.9; P = .003), which Dr. Spahillari calls “a low to intermediate rate suggesting a decreased sensitivity of the task force recommendations in identifying participants at risk of atherosclerotic cardiovascular disease.”

And what about CAC levels? Task force guidelines identified 404 of 732 (55.2%) African Americans with coronary calcium; ACC/AHA guidelines identified 507 (69.3%).

“Participants eligible for statins under the ACC/AHA guidelines who had CAC were at higher risk than those without CAC,” Dr. Spahillari said. Specifically, among those deemed eligible for statins by the ACC/AHA recommendations, the 10-year event rate per 1,000 person-years was 8.1 (95% CI, 5.9-11.1) in those with CAC and 3.1 (95% CI, 1.6-5.9) in those without CAC (P = .02).

The situation was different under the task force guidelines. CAC didn’t significantly affect the risk in those deemed eligible for statins by the task force guidelines, but it did seem to boost risk in those who weren’t statin eligible, she said.

Among those deemed not statin eligible by the task force guidelines, the event rate per 1,000 person-years was 2.8 in those with CAC (95% CI, 1.5-5.4) and 0.8 in those without (95%, CI 0.3-1.7) (P = .03).

How could CAC levels be useful for physicians? “As the role of CAC measurement is evolving, our findings support that measurement of CAC in an African-American population with an intermediate risk score would be clinically useful,” Dr. Spahillari said.

When ACC/AHA guidelines are used, she said, “the absence of CAC may reduce the number of individuals indicated for treatment with statins by ACC/AHA recommendations and temper concerns for overtreatment.”

What if a physician uses the task force guidelines in this population? “The presence of CAC may push a recommendation for statin treatment in individuals who would otherwise not be indicated for statins,” she said.

The National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities funded the study. One author reported funding from a National Institutes of Health grant. The others had no disclosures.

WASHINGTON – Using fractional flow reserve (FFR) to revascularize noninfarct coronary arteries during percutaneous coronary intervention (PCI) significantly reduced the subsequent 1-year risk of major adverse cardiovascular events among patients with ST-segment myocardial infarction and multivessel disease, according to the results of a randomized, multicenter trial.

Only 23 patients (8%) who underwent complete FFR-guided revascularization died or had a nonfatal myocardial infarction, cerebrovascular event, or repeat revascularization within a year of treatment, compared with 121 (20.5%) patients who underwent infarct-only treatment (hazard ratio, 0.35; 95% confidence interval, 0.22-0.55; P less than .001), Pieter C. Smits, MD, PhD, reported during a late-breaker session at the annual meeting of the American College of Cardiology.

Compared with infarct-only treatment, complete revascularization was associated with lower, but statistically similar, rates of mortality (1.7% vs. 1.4%; HR, 0.80; 95% CI, 0.25-2.6; P = .7), nonfatal myocardial infarction (4.7% vs. 2.4%; HR, 0.5; 95% CI, 0.2-1.1; P = .1), and cerebrovascular events (0.7% vs. 0%). The study lacked power to detect differences in rates of these uncommon events, the researchers noted.

In the infarct-only treatment group, stable or unstable angina accounted for most repeat revascularizations, about 80% of which were clinically indicated based on the study protocol, according to the researchers. Performing FFR-guided revascularization during primary PCI prevents sequential catheterizations and can potentially save costs by reducing predischarge stress tests, they commented. In their study, 12% of patients in the infarct-only group underwent stress tests, compared with 7% of those who underwent FFR-guided revascularization (P = .03).

Two patients experienced a serious adverse event related to FFR, the investigators noted. In one case, the FFR wire caused a dissection in the noninfarcted right coronary artery. The artery subsequently infarcted and the patient died in the hospital. Another patient developed an occlusion of the noninfarcted left anterior descending coronary artery. The patient developed ST-segment elevation and recurrent chest pain, but underwent successful PCI of the artery. There were no other adverse events except for brief episodes of atrioventricular conduction delay and episodes of moderate hypotension, they wrote.

This was an open-label study, and it is possible that patients and physicians in the infarct-only group were biased toward subsequent revascularizations because they knew the angiography results, the researchers also noted.

Maasstad Cardiovascular Research funded the study with unrestricted grants from Abbott Vascular and St. Jude Medical. Dr. Smits disclosed grant support from Abbott Vascular and St. Jude Medical, and grants support and personal fees from both entities outside the submitted work. 

WASHINGTON – Using fractional flow reserve (FFR) to revascularize noninfarct coronary arteries during percutaneous coronary intervention (PCI) significantly reduced the subsequent 1-year risk of major adverse cardiovascular events among patients with ST-segment myocardial infarction and multivessel disease, according to the results of a randomized, multicenter trial.

Only 23 patients (8%) who underwent complete FFR-guided revascularization died or had a nonfatal myocardial infarction, cerebrovascular event, or repeat revascularization within a year of treatment, compared with 121 (20.5%) patients who underwent infarct-only treatment (hazard ratio, 0.35; 95% confidence interval, 0.22-0.55; P less than .001), Pieter C. Smits, MD, PhD, reported during a late-breaker session at the annual meeting of the American College of Cardiology.

Compared with infarct-only treatment, complete revascularization was associated with lower, but statistically similar, rates of mortality (1.7% vs. 1.4%; HR, 0.80; 95% CI, 0.25-2.6; P = .7), nonfatal myocardial infarction (4.7% vs. 2.4%; HR, 0.5; 95% CI, 0.2-1.1; P = .1), and cerebrovascular events (0.7% vs. 0%). The study lacked power to detect differences in rates of these uncommon events, the researchers noted.

In the infarct-only treatment group, stable or unstable angina accounted for most repeat revascularizations, about 80% of which were clinically indicated based on the study protocol, according to the researchers. Performing FFR-guided revascularization during primary PCI prevents sequential catheterizations and can potentially save costs by reducing predischarge stress tests, they commented. In their study, 12% of patients in the infarct-only group underwent stress tests, compared with 7% of those who underwent FFR-guided revascularization (P = .03).

Two patients experienced a serious adverse event related to FFR, the investigators noted. In one case, the FFR wire caused a dissection in the noninfarcted right coronary artery. The artery subsequently infarcted and the patient died in the hospital. Another patient developed an occlusion of the noninfarcted left anterior descending coronary artery. The patient developed ST-segment elevation and recurrent chest pain, but underwent successful PCI of the artery. There were no other adverse events except for brief episodes of atrioventricular conduction delay and episodes of moderate hypotension, they wrote.

This was an open-label study, and it is possible that patients and physicians in the infarct-only group were biased toward subsequent revascularizations because they knew the angiography results, the researchers also noted.

Maasstad Cardiovascular Research funded the study with unrestricted grants from Abbott Vascular and St. Jude Medical. Dr. Smits disclosed grant support from Abbott Vascular and St. Jude Medical, and grants support and personal fees from both entities outside the submitted work. 

WASHINGTON – Using fractional flow reserve (FFR) to revascularize noninfarct coronary arteries during percutaneous coronary intervention (PCI) significantly reduced the subsequent 1-year risk of major adverse cardiovascular events among patients with ST-segment myocardial infarction and multivessel disease, according to the results of a randomized, multicenter trial.

Only 23 patients (8%) who underwent complete FFR-guided revascularization died or had a nonfatal myocardial infarction, cerebrovascular event, or repeat revascularization within a year of treatment, compared with 121 (20.5%) patients who underwent infarct-only treatment (hazard ratio, 0.35; 95% confidence interval, 0.22-0.55; P less than .001), Pieter C. Smits, MD, PhD, reported during a late-breaker session at the annual meeting of the American College of Cardiology.

Compared with infarct-only treatment, complete revascularization was associated with lower, but statistically similar, rates of mortality (1.7% vs. 1.4%; HR, 0.80; 95% CI, 0.25-2.6; P = .7), nonfatal myocardial infarction (4.7% vs. 2.4%; HR, 0.5; 95% CI, 0.2-1.1; P = .1), and cerebrovascular events (0.7% vs. 0%). The study lacked power to detect differences in rates of these uncommon events, the researchers noted.

In the infarct-only treatment group, stable or unstable angina accounted for most repeat revascularizations, about 80% of which were clinically indicated based on the study protocol, according to the researchers. Performing FFR-guided revascularization during primary PCI prevents sequential catheterizations and can potentially save costs by reducing predischarge stress tests, they commented. In their study, 12% of patients in the infarct-only group underwent stress tests, compared with 7% of those who underwent FFR-guided revascularization (P = .03).

Two patients experienced a serious adverse event related to FFR, the investigators noted. In one case, the FFR wire caused a dissection in the noninfarcted right coronary artery. The artery subsequently infarcted and the patient died in the hospital. Another patient developed an occlusion of the noninfarcted left anterior descending coronary artery. The patient developed ST-segment elevation and recurrent chest pain, but underwent successful PCI of the artery. There were no other adverse events except for brief episodes of atrioventricular conduction delay and episodes of moderate hypotension, they wrote.

This was an open-label study, and it is possible that patients and physicians in the infarct-only group were biased toward subsequent revascularizations because they knew the angiography results, the researchers also noted.

Maasstad Cardiovascular Research funded the study with unrestricted grants from Abbott Vascular and St. Jude Medical. Dr. Smits disclosed grant support from Abbott Vascular and St. Jude Medical, and grants support and personal fees from both entities outside the submitted work. 

WASHINGTON – A regimen of moderately intense exercise for 16 weeks produced no adverse effects and led to a clinically meaningful improvement in exercise capacity in a multicenter, randomized trial involving 136 patients with hypertrophic cardiomyopathy.

While finding that regular exercise produced a statistically significant improvement, compared with control patients fulfilled the study’s primary endpoint, it was perhaps as important that patients with hypertrophic cardiomyopathy (HCM) randomized to the exercise arm experienced no ill effects, a finding that bucked conventional wisdom that, once diagnosed, HCM patients must adhere to a largely inactive lifestyle.

Mitchel L. Zoler/Frontline Medical News

Mitchel L. Zoler/Frontline Medical News

[email protected]

On Twitter @mitchelzoler

WASHINGTON – A regimen of moderately intense exercise for 16 weeks produced no adverse effects and led to a clinically meaningful improvement in exercise capacity in a multicenter, randomized trial involving 136 patients with hypertrophic cardiomyopathy.

While finding that regular exercise produced a statistically significant improvement, compared with control patients fulfilled the study’s primary endpoint, it was perhaps as important that patients with hypertrophic cardiomyopathy (HCM) randomized to the exercise arm experienced no ill effects, a finding that bucked conventional wisdom that, once diagnosed, HCM patients must adhere to a largely inactive lifestyle.

Mitchel L. Zoler/Frontline Medical News

Mitchel L. Zoler/Frontline Medical News

[email protected]

On Twitter @mitchelzoler

WASHINGTON – A regimen of moderately intense exercise for 16 weeks produced no adverse effects and led to a clinically meaningful improvement in exercise capacity in a multicenter, randomized trial involving 136 patients with hypertrophic cardiomyopathy.

While finding that regular exercise produced a statistically significant improvement, compared with control patients fulfilled the study’s primary endpoint, it was perhaps as important that patients with hypertrophic cardiomyopathy (HCM) randomized to the exercise arm experienced no ill effects, a finding that bucked conventional wisdom that, once diagnosed, HCM patients must adhere to a largely inactive lifestyle.

Mitchel L. Zoler/Frontline Medical News

Mitchel L. Zoler/Frontline Medical News

[email protected]

On Twitter @mitchelzoler

WASHINGTON – Application clear graphic nutrition labels on the front of packaged foods could help patients make healthier food choices, according to a study out of the George Institute of Global Health, Sydney.

Bruce Neal, PhD, senior director of the food policy division at the institute, and his colleagues asked 1,578 study participants to use a smart phone scanner to record the packaged foods they bought over the course of a week. Nutrition information from those scans was used to derive a nutrient profile score and plugged into four different food labeling systems on a randomized basis:

• Health Star Rating (HSR). A graphic label that gives the product from one to five stars.
• Multi-color Traffic Light (MTD). A graphic label that advises the participant to stop, use caution, or go.
• Daily Intake Guide (DIG). A graphic label that presents important nutrients in larger numbers.
• Nutrient Information Panel (NIP). A chart-based label listing nutrient values, similar to the U.S. Nutrition Facts label.

Nutrient information provided by HSR was found to be noninferior to the alternatives, Dr. Neal said at the annual meeting of the American College of Cardiology.

HSR earned a superiority score of 0.38, 0.1, and 0.23 when compared with MTL, DIG, and NIP labels, respectively, according to the study.

[email protected]
On Twitter @EAZtweets

WASHINGTON – Application clear graphic nutrition labels on the front of packaged foods could help patients make healthier food choices, according to a study out of the George Institute of Global Health, Sydney.

Bruce Neal, PhD, senior director of the food policy division at the institute, and his colleagues asked 1,578 study participants to use a smart phone scanner to record the packaged foods they bought over the course of a week. Nutrition information from those scans was used to derive a nutrient profile score and plugged into four different food labeling systems on a randomized basis:

• Health Star Rating (HSR). A graphic label that gives the product from one to five stars.
• Multi-color Traffic Light (MTD). A graphic label that advises the participant to stop, use caution, or go.
• Daily Intake Guide (DIG). A graphic label that presents important nutrients in larger numbers.
• Nutrient Information Panel (NIP). A chart-based label listing nutrient values, similar to the U.S. Nutrition Facts label.

Nutrient information provided by HSR was found to be noninferior to the alternatives, Dr. Neal said at the annual meeting of the American College of Cardiology.

HSR earned a superiority score of 0.38, 0.1, and 0.23 when compared with MTL, DIG, and NIP labels, respectively, according to the study.

[email protected]
On Twitter @EAZtweets

WASHINGTON – Application clear graphic nutrition labels on the front of packaged foods could help patients make healthier food choices, according to a study out of the George Institute of Global Health, Sydney.

Bruce Neal, PhD, senior director of the food policy division at the institute, and his colleagues asked 1,578 study participants to use a smart phone scanner to record the packaged foods they bought over the course of a week. Nutrition information from those scans was used to derive a nutrient profile score and plugged into four different food labeling systems on a randomized basis:

• Health Star Rating (HSR). A graphic label that gives the product from one to five stars.
• Multi-color Traffic Light (MTD). A graphic label that advises the participant to stop, use caution, or go.
• Daily Intake Guide (DIG). A graphic label that presents important nutrients in larger numbers.
• Nutrient Information Panel (NIP). A chart-based label listing nutrient values, similar to the U.S. Nutrition Facts label.

Nutrient information provided by HSR was found to be noninferior to the alternatives, Dr. Neal said at the annual meeting of the American College of Cardiology.

HSR earned a superiority score of 0.38, 0.1, and 0.23 when compared with MTL, DIG, and NIP labels, respectively, according to the study.

[email protected]
On Twitter @EAZtweets

Using transcatheter aortic valve replacement (TAVR) to treat bicuspid aortic valve stenosis (AS) can be significantly less effective than using TAVR to treat tricuspid AS, according to the findings of a new study presented at the annual meeting of the American College of Cardiology and published simultaneously in the Journal of the American College of Cardiology.

“There is a paucity of data comparing the clinical outcomes of TAVR in bicuspid and tricuspid AS,” wrote the authors of the study, led by Sung-Han Yoon, MD, of the Cedars-Sinai Heart Institute in Los Angeles. “Given the increasing frequency of bicuspid AS in younger patients, coupled with the worldwide shift of treating younger and lower–surgical-risk patients with TAVR, the clinical outcomes of TAVR in bicuspid AS warrants special attention.”

Dr. Yoon and his coinvestigators began by collecting data from the Bicuspid AS TAVR registry, which began in December 2013 and contains information on patients from 33 health care centers around the world. Patients who entered the database prior to the initiation of the study were screened retroactively, while those who joined afterward were followed prospectively.

Eventually, 561 bicuspid AS patients were included in the study, out of a total of 576 that were treated between April 2005 and May 2016. Twelve centers also performed tricuspid AS, with investigators able to collect data on 5,900 patients who underwent the procedure during the same period of time. Ultimately, 4,546 were included in the study.

“Given the differences in baseline clinical, echocardiographic, and procedural characteristics between patients with bicuspid and tricuspid AS, propensity-score matching was applied to identify a cohort of patients with similar baseline characteristics, and thus clinical outcomes of propensity-score matched cohorts were compared,” the authors explained.

Variables used when establishing propensity-score matches included age, sex, New York Heart Association functional class III or IV, the presence of certain conditions such as chronic lung disease and diabetes, and procedural data. Dr. Yoon and his colleagues were able to create 546 pairs of matched patients between the bicuspid AS and tricuspid AS cohorts.

The devices implanted in subjects also underwent classification by the investigators, either as early-generation or new-generation devices. The former consisted of Sapien XT and CoreValve devices, while Sapien 3, Lotus, and Evolut R devices comprised the latter classification. A total of 320 bicuspid AS and 321 tricuspid AS patients received early-generation implant devices, with 226 and 225 patients, respectively, receiving new-generation devices.

Devices were less successful in bicuspid AS patients versus tricuspid AS patients: 85.3% and 91.4%, respectively (P = .002). Furthermore, a significantly higher rate of bicuspid AS patients had to be converted to surgery, compared with tricuspid AS patients: 2.0% and 0.2%, respectively (P = .006). Early-generation implant devices had considerably higher rates of issues in bicuspid AS patients, with 4.5% of those receiving Sapien XT experiencing aortic root injury and 0% of tricuspid AS patients with the same device having the same problem (P = .015). Bicuspid AS patients who received the CoreValve implant experienced paravalvular leak 19.4% of the time, compared with 10.5% in tricuspid AS patients (P = .02); these leaks were classified as “moderate to severe.”

“In addition, patients with bicuspid AS had more frequent second valve implantation (11.6% vs. 2.9%; P = .002) [and] subsequent lower device success rates (72.1% vs. 86.0%; P = .002) than those with tricuspid AS when receiving the CoreValve,” the authors noted. “However, there were no significant differences in these adverse procedural events between groups when receiving the Sapien 3 and Lotus.”

There were also no significant differences between the bicuspid and tricuspid AS in terms of mortality rates. At 2 years postoperation, all-cause mortality rates were 17.2% for bicuspid AS patients and 19.4% for tricuspid AS patients, regardless of the type of device implant (P = .28). When comparing early and new-generation devices, results were similarly nonsignificant: early-generation bicuspid vs. tricuspid AS all-cause mortality rates were 14.5% and 13.7%, respectively (P = .80) and 4.5% vs. 7.4% (P = .64) for new-generation devices.

“The present study is the first large-scale study that compared the safety, efficacy, and clinical outcomes of TAVR in patients with bicuspid and tricuspid AS,” Dr. Yoon and his colleagues noted, adding that, in regards to the disparity in device effectiveness, “The present study showed that the initial attempt of device advancement succeeded in overcoming the procedural limitations in tricuspid AS and now go beyond the challenges in treating bicuspid AS.”

No funding source for this study was disclosed. Dr. Yoon did not report any relevant financial disclosures, but several coauthors disclosed potentially relevant financial conflicts.

[email protected]

Using transcatheter aortic valve replacement (TAVR) to treat bicuspid aortic valve stenosis (AS) can be significantly less effective than using TAVR to treat tricuspid AS, according to the findings of a new study presented at the annual meeting of the American College of Cardiology and published simultaneously in the Journal of the American College of Cardiology.

“There is a paucity of data comparing the clinical outcomes of TAVR in bicuspid and tricuspid AS,” wrote the authors of the study, led by Sung-Han Yoon, MD, of the Cedars-Sinai Heart Institute in Los Angeles. “Given the increasing frequency of bicuspid AS in younger patients, coupled with the worldwide shift of treating younger and lower–surgical-risk patients with TAVR, the clinical outcomes of TAVR in bicuspid AS warrants special attention.”

Dr. Yoon and his coinvestigators began by collecting data from the Bicuspid AS TAVR registry, which began in December 2013 and contains information on patients from 33 health care centers around the world. Patients who entered the database prior to the initiation of the study were screened retroactively, while those who joined afterward were followed prospectively.

Eventually, 561 bicuspid AS patients were included in the study, out of a total of 576 that were treated between April 2005 and May 2016. Twelve centers also performed tricuspid AS, with investigators able to collect data on 5,900 patients who underwent the procedure during the same period of time. Ultimately, 4,546 were included in the study.

“Given the differences in baseline clinical, echocardiographic, and procedural characteristics between patients with bicuspid and tricuspid AS, propensity-score matching was applied to identify a cohort of patients with similar baseline characteristics, and thus clinical outcomes of propensity-score matched cohorts were compared,” the authors explained.

Variables used when establishing propensity-score matches included age, sex, New York Heart Association functional class III or IV, the presence of certain conditions such as chronic lung disease and diabetes, and procedural data. Dr. Yoon and his colleagues were able to create 546 pairs of matched patients between the bicuspid AS and tricuspid AS cohorts.

The devices implanted in subjects also underwent classification by the investigators, either as early-generation or new-generation devices. The former consisted of Sapien XT and CoreValve devices, while Sapien 3, Lotus, and Evolut R devices comprised the latter classification. A total of 320 bicuspid AS and 321 tricuspid AS patients received early-generation implant devices, with 226 and 225 patients, respectively, receiving new-generation devices.

Devices were less successful in bicuspid AS patients versus tricuspid AS patients: 85.3% and 91.4%, respectively (P = .002). Furthermore, a significantly higher rate of bicuspid AS patients had to be converted to surgery, compared with tricuspid AS patients: 2.0% and 0.2%, respectively (P = .006). Early-generation implant devices had considerably higher rates of issues in bicuspid AS patients, with 4.5% of those receiving Sapien XT experiencing aortic root injury and 0% of tricuspid AS patients with the same device having the same problem (P = .015). Bicuspid AS patients who received the CoreValve implant experienced paravalvular leak 19.4% of the time, compared with 10.5% in tricuspid AS patients (P = .02); these leaks were classified as “moderate to severe.”

“In addition, patients with bicuspid AS had more frequent second valve implantation (11.6% vs. 2.9%; P = .002) [and] subsequent lower device success rates (72.1% vs. 86.0%; P = .002) than those with tricuspid AS when receiving the CoreValve,” the authors noted. “However, there were no significant differences in these adverse procedural events between groups when receiving the Sapien 3 and Lotus.”

There were also no significant differences between the bicuspid and tricuspid AS in terms of mortality rates. At 2 years postoperation, all-cause mortality rates were 17.2% for bicuspid AS patients and 19.4% for tricuspid AS patients, regardless of the type of device implant (P = .28). When comparing early and new-generation devices, results were similarly nonsignificant: early-generation bicuspid vs. tricuspid AS all-cause mortality rates were 14.5% and 13.7%, respectively (P = .80) and 4.5% vs. 7.4% (P = .64) for new-generation devices.

“The present study is the first large-scale study that compared the safety, efficacy, and clinical outcomes of TAVR in patients with bicuspid and tricuspid AS,” Dr. Yoon and his colleagues noted, adding that, in regards to the disparity in device effectiveness, “The present study showed that the initial attempt of device advancement succeeded in overcoming the procedural limitations in tricuspid AS and now go beyond the challenges in treating bicuspid AS.”

No funding source for this study was disclosed. Dr. Yoon did not report any relevant financial disclosures, but several coauthors disclosed potentially relevant financial conflicts.

[email protected]

Using transcatheter aortic valve replacement (TAVR) to treat bicuspid aortic valve stenosis (AS) can be significantly less effective than using TAVR to treat tricuspid AS, according to the findings of a new study presented at the annual meeting of the American College of Cardiology and published simultaneously in the Journal of the American College of Cardiology.

“There is a paucity of data comparing the clinical outcomes of TAVR in bicuspid and tricuspid AS,” wrote the authors of the study, led by Sung-Han Yoon, MD, of the Cedars-Sinai Heart Institute in Los Angeles. “Given the increasing frequency of bicuspid AS in younger patients, coupled with the worldwide shift of treating younger and lower–surgical-risk patients with TAVR, the clinical outcomes of TAVR in bicuspid AS warrants special attention.”

Dr. Yoon and his coinvestigators began by collecting data from the Bicuspid AS TAVR registry, which began in December 2013 and contains information on patients from 33 health care centers around the world. Patients who entered the database prior to the initiation of the study were screened retroactively, while those who joined afterward were followed prospectively.

Eventually, 561 bicuspid AS patients were included in the study, out of a total of 576 that were treated between April 2005 and May 2016. Twelve centers also performed tricuspid AS, with investigators able to collect data on 5,900 patients who underwent the procedure during the same period of time. Ultimately, 4,546 were included in the study.

“Given the differences in baseline clinical, echocardiographic, and procedural characteristics between patients with bicuspid and tricuspid AS, propensity-score matching was applied to identify a cohort of patients with similar baseline characteristics, and thus clinical outcomes of propensity-score matched cohorts were compared,” the authors explained.

Variables used when establishing propensity-score matches included age, sex, New York Heart Association functional class III or IV, the presence of certain conditions such as chronic lung disease and diabetes, and procedural data. Dr. Yoon and his colleagues were able to create 546 pairs of matched patients between the bicuspid AS and tricuspid AS cohorts.

The devices implanted in subjects also underwent classification by the investigators, either as early-generation or new-generation devices. The former consisted of Sapien XT and CoreValve devices, while Sapien 3, Lotus, and Evolut R devices comprised the latter classification. A total of 320 bicuspid AS and 321 tricuspid AS patients received early-generation implant devices, with 226 and 225 patients, respectively, receiving new-generation devices.

Devices were less successful in bicuspid AS patients versus tricuspid AS patients: 85.3% and 91.4%, respectively (P = .002). Furthermore, a significantly higher rate of bicuspid AS patients had to be converted to surgery, compared with tricuspid AS patients: 2.0% and 0.2%, respectively (P = .006). Early-generation implant devices had considerably higher rates of issues in bicuspid AS patients, with 4.5% of those receiving Sapien XT experiencing aortic root injury and 0% of tricuspid AS patients with the same device having the same problem (P = .015). Bicuspid AS patients who received the CoreValve implant experienced paravalvular leak 19.4% of the time, compared with 10.5% in tricuspid AS patients (P = .02); these leaks were classified as “moderate to severe.”

“In addition, patients with bicuspid AS had more frequent second valve implantation (11.6% vs. 2.9%; P = .002) [and] subsequent lower device success rates (72.1% vs. 86.0%; P = .002) than those with tricuspid AS when receiving the CoreValve,” the authors noted. “However, there were no significant differences in these adverse procedural events between groups when receiving the Sapien 3 and Lotus.”

There were also no significant differences between the bicuspid and tricuspid AS in terms of mortality rates. At 2 years postoperation, all-cause mortality rates were 17.2% for bicuspid AS patients and 19.4% for tricuspid AS patients, regardless of the type of device implant (P = .28). When comparing early and new-generation devices, results were similarly nonsignificant: early-generation bicuspid vs. tricuspid AS all-cause mortality rates were 14.5% and 13.7%, respectively (P = .80) and 4.5% vs. 7.4% (P = .64) for new-generation devices.

“The present study is the first large-scale study that compared the safety, efficacy, and clinical outcomes of TAVR in patients with bicuspid and tricuspid AS,” Dr. Yoon and his colleagues noted, adding that, in regards to the disparity in device effectiveness, “The present study showed that the initial attempt of device advancement succeeded in overcoming the procedural limitations in tricuspid AS and now go beyond the challenges in treating bicuspid AS.”

No funding source for this study was disclosed. Dr. Yoon did not report any relevant financial disclosures, but several coauthors disclosed potentially relevant financial conflicts.

[email protected]

Clinically significant bleeding in acute coronary patients was approximately 5% when their P2Y12 inhibitor treatment was combined with either rivaroxaban or with aspirin, based on data from a randomized, multicenter study of 3,037 adults.

The findings support the use of low-dose rivaroxaban as a safe strategy and an alternative to aspirin for postacute care of coronary syndromes, wrote E. Magnus Ohman, MD, of Duke University in Durham, N.C., and his colleagues.

The study was presented at the annual meeting of the American College of Cardiology and published simultaneously in the Lancet (2017. Mar 18. doi: org/10.1016/S0140-6736[17]30751-1).

The GEMINI ACS 1 trial included patients older than 18 years, who were randomized to P2Y12 with rivaroxaban or P2Y12 with aspirin within 10 days of admission for acute coronary syndrome events, from 371 clinical centers in 21 countries. The patients received 2.5 mg of low-dose rivaroxaban twice daily plus a P2Y12 inhibitor (clopidogrel or ticagrelor, based on national availability) or 100 mg of aspirin daily plus a P2Y12 inhibitor. Patients were assessed at 30, 90, 180, and 270 days.

Overall, 154 patients (5%) met the primary endpoint of thrombolysis in myocardial infarction (TIMI) of clinically significant bleeding – 80 patients (5%) in the rivaroxaban group and 74 (5%) in the aspirin group. Baseline demographics were not significantly different between the groups, and clinically significant bleeding was not significantly different among subgroups.

TIMI bleeding that required medical attention was the most common, occurring in 4% of each group. Both groups had a low frequency of severe or major bleeding based on the TIMI bleeding definitions, the researchers noted.

The composite ischemic endpoint of cardiovascular death, myocardial infarction, stroke, or definite stent thrombosis was 5% in both groups, and both groups had a similar frequency of all-cause mortality and of each of the composite ischemic elements. Rivaroxaban was associated with a higher occurrence of the ischemic composite endpoint in the first 30 days (hazard ratio, 1.48), but this difference was not statistically significant.

“Additionally, no significant interaction was noted for the risk of clinically significant bleeding by P2Y12 inhibitor strata (ticagrelor vs. clopidogrel), but these stratified bleeding analyses were exploratory and hypothesis generating,” the researchers wrote.

The findings were limited by several factors, including a delay in randomization from the patients’ index events, a homogeneous population, and exclusion of patients treated with prasugrel, the researchers noted. However, “based upon these findings and the unmet need for improved treatments in the postacute coronary syndromes setting, further testing of the efficacy and safety of this novel dual pathway antithrombotic regimen in an adequately powered trial should be considered,” they said.

The study was funded by Janssen Research & Development and Bayer. Lead author Dr. Ohman has received research grants from Janssen and other companies. Several coauthors disclosed relationships with multiple companies, including Janssen.

Clinically significant bleeding in acute coronary patients was approximately 5% when their P2Y12 inhibitor treatment was combined with either rivaroxaban or with aspirin, based on data from a randomized, multicenter study of 3,037 adults.

The findings support the use of low-dose rivaroxaban as a safe strategy and an alternative to aspirin for postacute care of coronary syndromes, wrote E. Magnus Ohman, MD, of Duke University in Durham, N.C., and his colleagues.

The study was presented at the annual meeting of the American College of Cardiology and published simultaneously in the Lancet (2017. Mar 18. doi: org/10.1016/S0140-6736[17]30751-1).

The GEMINI ACS 1 trial included patients older than 18 years, who were randomized to P2Y12 with rivaroxaban or P2Y12 with aspirin within 10 days of admission for acute coronary syndrome events, from 371 clinical centers in 21 countries. The patients received 2.5 mg of low-dose rivaroxaban twice daily plus a P2Y12 inhibitor (clopidogrel or ticagrelor, based on national availability) or 100 mg of aspirin daily plus a P2Y12 inhibitor. Patients were assessed at 30, 90, 180, and 270 days.

Overall, 154 patients (5%) met the primary endpoint of thrombolysis in myocardial infarction (TIMI) of clinically significant bleeding – 80 patients (5%) in the rivaroxaban group and 74 (5%) in the aspirin group. Baseline demographics were not significantly different between the groups, and clinically significant bleeding was not significantly different among subgroups.

TIMI bleeding that required medical attention was the most common, occurring in 4% of each group. Both groups had a low frequency of severe or major bleeding based on the TIMI bleeding definitions, the researchers noted.

The composite ischemic endpoint of cardiovascular death, myocardial infarction, stroke, or definite stent thrombosis was 5% in both groups, and both groups had a similar frequency of all-cause mortality and of each of the composite ischemic elements. Rivaroxaban was associated with a higher occurrence of the ischemic composite endpoint in the first 30 days (hazard ratio, 1.48), but this difference was not statistically significant.

“Additionally, no significant interaction was noted for the risk of clinically significant bleeding by P2Y12 inhibitor strata (ticagrelor vs. clopidogrel), but these stratified bleeding analyses were exploratory and hypothesis generating,” the researchers wrote.

The findings were limited by several factors, including a delay in randomization from the patients’ index events, a homogeneous population, and exclusion of patients treated with prasugrel, the researchers noted. However, “based upon these findings and the unmet need for improved treatments in the postacute coronary syndromes setting, further testing of the efficacy and safety of this novel dual pathway antithrombotic regimen in an adequately powered trial should be considered,” they said.

The study was funded by Janssen Research & Development and Bayer. Lead author Dr. Ohman has received research grants from Janssen and other companies. Several coauthors disclosed relationships with multiple companies, including Janssen.

Clinically significant bleeding in acute coronary patients was approximately 5% when their P2Y12 inhibitor treatment was combined with either rivaroxaban or with aspirin, based on data from a randomized, multicenter study of 3,037 adults.

The findings support the use of low-dose rivaroxaban as a safe strategy and an alternative to aspirin for postacute care of coronary syndromes, wrote E. Magnus Ohman, MD, of Duke University in Durham, N.C., and his colleagues.

The study was presented at the annual meeting of the American College of Cardiology and published simultaneously in the Lancet (2017. Mar 18. doi: org/10.1016/S0140-6736[17]30751-1).

The GEMINI ACS 1 trial included patients older than 18 years, who were randomized to P2Y12 with rivaroxaban or P2Y12 with aspirin within 10 days of admission for acute coronary syndrome events, from 371 clinical centers in 21 countries. The patients received 2.5 mg of low-dose rivaroxaban twice daily plus a P2Y12 inhibitor (clopidogrel or ticagrelor, based on national availability) or 100 mg of aspirin daily plus a P2Y12 inhibitor. Patients were assessed at 30, 90, 180, and 270 days.

Overall, 154 patients (5%) met the primary endpoint of thrombolysis in myocardial infarction (TIMI) of clinically significant bleeding – 80 patients (5%) in the rivaroxaban group and 74 (5%) in the aspirin group. Baseline demographics were not significantly different between the groups, and clinically significant bleeding was not significantly different among subgroups.

TIMI bleeding that required medical attention was the most common, occurring in 4% of each group. Both groups had a low frequency of severe or major bleeding based on the TIMI bleeding definitions, the researchers noted.

The composite ischemic endpoint of cardiovascular death, myocardial infarction, stroke, or definite stent thrombosis was 5% in both groups, and both groups had a similar frequency of all-cause mortality and of each of the composite ischemic elements. Rivaroxaban was associated with a higher occurrence of the ischemic composite endpoint in the first 30 days (hazard ratio, 1.48), but this difference was not statistically significant.

“Additionally, no significant interaction was noted for the risk of clinically significant bleeding by P2Y12 inhibitor strata (ticagrelor vs. clopidogrel), but these stratified bleeding analyses were exploratory and hypothesis generating,” the researchers wrote.

The findings were limited by several factors, including a delay in randomization from the patients’ index events, a homogeneous population, and exclusion of patients treated with prasugrel, the researchers noted. However, “based upon these findings and the unmet need for improved treatments in the postacute coronary syndromes setting, further testing of the efficacy and safety of this novel dual pathway antithrombotic regimen in an adequately powered trial should be considered,” they said.

The study was funded by Janssen Research & Development and Bayer. Lead author Dr. Ohman has received research grants from Janssen and other companies. Several coauthors disclosed relationships with multiple companies, including Janssen.

In patients with venous thromboembolism at equipoise for further anticoagulation therapy, treatment with a 10-mg dose of rivaroxaban (Xarelto) had comparable efficacy to a 20-mg dose, with both leading to fewer recurrences than treatment with aspirin. There were no statistically significant differences in clinically relevant nonmajor bleeding between the three groups.

The study’s conclusions are limited to relatively healthy patients such as the ones who were selected for the study.

The findings were presented at the annual meeting of the American College of Cardiology and published simultaneously in the New England Journal of Medicine (N Engl J Med 2017 March 18. doi: 10.1056/NEJMoa1700518).

Anticoagulants are the primary treatment for prevention of venous thromboembolism recurrences, but the medications are often stopped after 6-12 months because of concerns about bleeding. To counter that issue, physicians may prescribe lower doses of anticoagulants such as rivaroxaban, or substitute aspirin.

The work follows another recent study of apixaban (Eliquis), which showed that a 2.5-mg twice-daily dose performed the same as did a 5.0-mg twice-daily dose in the prevention of venous thromboembolism recurrence (N Engl J Med. 2013;368[8]:699-708).

“I think the story is kind of the same here,” said David Garcia, MD, professor of hematology at the University of Washington, Seattle, who was one of the principal investigators in the trial.

Patients with unprompted venous thromboembolism are increasingly being offered anticoagulant therapy to prevent recurrences. Those drugs have inherent bleeding risks, but the newer drugs and even warfarin are becoming safer. Even so, “as we embark on that, one has to remember that the risk of anticoagulants is cumulative. It may only carry a risk of 1% per year of major hemorrhage, but if the patient has to take it for 10 or 20 or 30 years, it’s a nontrivial risk of major bleeding over that time,” said Dr. Garcia.

The researchers conducted the Reduced-Dose Rivaroxaban in the Long-Term Prevention of Recurrent Symptomatic Venous Thromboembolism (EINSTEIN CHOICE) trial, in which 3,365 patients from 24 sites were randomized to receive 20 mg rivaroxaban, 10 mg rivaroxaban, or 100 mg aspirin for up to 1 year following an initial 6-12 months of treatment with anticoagulation therapy.

During a median follow-up of 1 year, 4.4% of patients on aspirin experienced a recurrence, compared with 1.5% of patients in the 20-mg rivaroxaban group (hazard ratio versus aspirin, 0.34; 95% confidence interval, 0.20-0.59; P less than .001), and 1.2% in the 10-mg rivaroxaban group (HR versus aspirin, 0.26; 95% CI, 0.14-0.47; P less than .001). There was no statistical significance between the two doses of rivaroxaban.

The rates of fatal thromboembolism were similar, at 0.2% in the 20-mg rivaroxaban group, 0% in the 10-mg group, and 0.2% in the aspirin group.

Major bleeding occurred in 0.5% of patients in the 20-mg rivaroxaban group, in 0.4% of the 10-mg rivaroxaban group, and 0.3% in the aspirin group. Nonmajor, clinically relevant bleeding was also similar between groups, at 2.7% in the 20-mg group, 2.0% in the 10-mg group, and 1.8% in the aspirin group. These differences were not statistically significant.

The study is good news for clinicians as they help patients decide whether to undergo preventive therapy. “Even before the newer agents arrived on the market, we had moved the needle a lot in terms of maximizing the safety of warfarin. I think these drugs take it to yet another level,” said Dr. Garcia.

Bayer Pharmaceuticals funded the study. Dr. Garcia has received honoraria from Bristol-Meyers Squibb, Pfizer, and Boehringer Ingelheim.

In patients with venous thromboembolism at equipoise for further anticoagulation therapy, treatment with a 10-mg dose of rivaroxaban (Xarelto) had comparable efficacy to a 20-mg dose, with both leading to fewer recurrences than treatment with aspirin. There were no statistically significant differences in clinically relevant nonmajor bleeding between the three groups.

The study’s conclusions are limited to relatively healthy patients such as the ones who were selected for the study.

The findings were presented at the annual meeting of the American College of Cardiology and published simultaneously in the New England Journal of Medicine (N Engl J Med 2017 March 18. doi: 10.1056/NEJMoa1700518).

Anticoagulants are the primary treatment for prevention of venous thromboembolism recurrences, but the medications are often stopped after 6-12 months because of concerns about bleeding. To counter that issue, physicians may prescribe lower doses of anticoagulants such as rivaroxaban, or substitute aspirin.

The work follows another recent study of apixaban (Eliquis), which showed that a 2.5-mg twice-daily dose performed the same as did a 5.0-mg twice-daily dose in the prevention of venous thromboembolism recurrence (N Engl J Med. 2013;368[8]:699-708).

“I think the story is kind of the same here,” said David Garcia, MD, professor of hematology at the University of Washington, Seattle, who was one of the principal investigators in the trial.

Patients with unprompted venous thromboembolism are increasingly being offered anticoagulant therapy to prevent recurrences. Those drugs have inherent bleeding risks, but the newer drugs and even warfarin are becoming safer. Even so, “as we embark on that, one has to remember that the risk of anticoagulants is cumulative. It may only carry a risk of 1% per year of major hemorrhage, but if the patient has to take it for 10 or 20 or 30 years, it’s a nontrivial risk of major bleeding over that time,” said Dr. Garcia.

The researchers conducted the Reduced-Dose Rivaroxaban in the Long-Term Prevention of Recurrent Symptomatic Venous Thromboembolism (EINSTEIN CHOICE) trial, in which 3,365 patients from 24 sites were randomized to receive 20 mg rivaroxaban, 10 mg rivaroxaban, or 100 mg aspirin for up to 1 year following an initial 6-12 months of treatment with anticoagulation therapy.

During a median follow-up of 1 year, 4.4% of patients on aspirin experienced a recurrence, compared with 1.5% of patients in the 20-mg rivaroxaban group (hazard ratio versus aspirin, 0.34; 95% confidence interval, 0.20-0.59; P less than .001), and 1.2% in the 10-mg rivaroxaban group (HR versus aspirin, 0.26; 95% CI, 0.14-0.47; P less than .001). There was no statistical significance between the two doses of rivaroxaban.

The rates of fatal thromboembolism were similar, at 0.2% in the 20-mg rivaroxaban group, 0% in the 10-mg group, and 0.2% in the aspirin group.

Major bleeding occurred in 0.5% of patients in the 20-mg rivaroxaban group, in 0.4% of the 10-mg rivaroxaban group, and 0.3% in the aspirin group. Nonmajor, clinically relevant bleeding was also similar between groups, at 2.7% in the 20-mg group, 2.0% in the 10-mg group, and 1.8% in the aspirin group. These differences were not statistically significant.

The study is good news for clinicians as they help patients decide whether to undergo preventive therapy. “Even before the newer agents arrived on the market, we had moved the needle a lot in terms of maximizing the safety of warfarin. I think these drugs take it to yet another level,” said Dr. Garcia.

Bayer Pharmaceuticals funded the study. Dr. Garcia has received honoraria from Bristol-Meyers Squibb, Pfizer, and Boehringer Ingelheim.

In patients with venous thromboembolism at equipoise for further anticoagulation therapy, treatment with a 10-mg dose of rivaroxaban (Xarelto) had comparable efficacy to a 20-mg dose, with both leading to fewer recurrences than treatment with aspirin. There were no statistically significant differences in clinically relevant nonmajor bleeding between the three groups.

The study’s conclusions are limited to relatively healthy patients such as the ones who were selected for the study.

The findings were presented at the annual meeting of the American College of Cardiology and published simultaneously in the New England Journal of Medicine (N Engl J Med 2017 March 18. doi: 10.1056/NEJMoa1700518).

Anticoagulants are the primary treatment for prevention of venous thromboembolism recurrences, but the medications are often stopped after 6-12 months because of concerns about bleeding. To counter that issue, physicians may prescribe lower doses of anticoagulants such as rivaroxaban, or substitute aspirin.

The work follows another recent study of apixaban (Eliquis), which showed that a 2.5-mg twice-daily dose performed the same as did a 5.0-mg twice-daily dose in the prevention of venous thromboembolism recurrence (N Engl J Med. 2013;368[8]:699-708).

“I think the story is kind of the same here,” said David Garcia, MD, professor of hematology at the University of Washington, Seattle, who was one of the principal investigators in the trial.

Patients with unprompted venous thromboembolism are increasingly being offered anticoagulant therapy to prevent recurrences. Those drugs have inherent bleeding risks, but the newer drugs and even warfarin are becoming safer. Even so, “as we embark on that, one has to remember that the risk of anticoagulants is cumulative. It may only carry a risk of 1% per year of major hemorrhage, but if the patient has to take it for 10 or 20 or 30 years, it’s a nontrivial risk of major bleeding over that time,” said Dr. Garcia.

The researchers conducted the Reduced-Dose Rivaroxaban in the Long-Term Prevention of Recurrent Symptomatic Venous Thromboembolism (EINSTEIN CHOICE) trial, in which 3,365 patients from 24 sites were randomized to receive 20 mg rivaroxaban, 10 mg rivaroxaban, or 100 mg aspirin for up to 1 year following an initial 6-12 months of treatment with anticoagulation therapy.

During a median follow-up of 1 year, 4.4% of patients on aspirin experienced a recurrence, compared with 1.5% of patients in the 20-mg rivaroxaban group (hazard ratio versus aspirin, 0.34; 95% confidence interval, 0.20-0.59; P less than .001), and 1.2% in the 10-mg rivaroxaban group (HR versus aspirin, 0.26; 95% CI, 0.14-0.47; P less than .001). There was no statistical significance between the two doses of rivaroxaban.

The rates of fatal thromboembolism were similar, at 0.2% in the 20-mg rivaroxaban group, 0% in the 10-mg group, and 0.2% in the aspirin group.

Major bleeding occurred in 0.5% of patients in the 20-mg rivaroxaban group, in 0.4% of the 10-mg rivaroxaban group, and 0.3% in the aspirin group. Nonmajor, clinically relevant bleeding was also similar between groups, at 2.7% in the 20-mg group, 2.0% in the 10-mg group, and 1.8% in the aspirin group. These differences were not statistically significant.

The study is good news for clinicians as they help patients decide whether to undergo preventive therapy. “Even before the newer agents arrived on the market, we had moved the needle a lot in terms of maximizing the safety of warfarin. I think these drugs take it to yet another level,” said Dr. Garcia.

Bayer Pharmaceuticals funded the study. Dr. Garcia has received honoraria from Bristol-Meyers Squibb, Pfizer, and Boehringer Ingelheim.

Washington – Heart teams will have more options when making treatment decisions for patients with severe aortic stenosis who are at intermediate risk, now that the results of the SURTAVI (Surgical Replacement and Transcatheter Aortic Valve Implantation) trial have been presented.

Those results showed that transcatheter aortic valve replacement (TAVR) in patients with severe aortic stenosis at intermediate risk was not only noninferior to surgical replacement, “but in my mind superior, because you don’t get your chest cracked, you get home earlier, and you have fewer strokes [in this trial], Roxana Mehran, MD, professor and director of interventional cardiovascular research at Mount Sinai Hospital in New York, said in a video interview at the annual meeting of the American College of Cardiology.

In SURTAVI, which used Medtronic’s self-expanding CoreValve and Evolut-R bioprostheses in 863 patients randomized to TAVR, 12.6% met the study’s primary endpoint – death from any cause or disabling stroke at 24 months – versus 14% of the 796 patients randomized to surgery, a statistically nonsignificant difference. Notably, the risk of any type of stroke at 30 days was statistically superior for TAVR, 3.4%, compared with 5.6% for surgical replacement.

“It’s tremendously important to see the change in how we’re going to be evaluating patients with aortic stenosis,” Dr. Mehran said.

[email protected]

Washington – Heart teams will have more options when making treatment decisions for patients with severe aortic stenosis who are at intermediate risk, now that the results of the SURTAVI (Surgical Replacement and Transcatheter Aortic Valve Implantation) trial have been presented.

Those results showed that transcatheter aortic valve replacement (TAVR) in patients with severe aortic stenosis at intermediate risk was not only noninferior to surgical replacement, “but in my mind superior, because you don’t get your chest cracked, you get home earlier, and you have fewer strokes [in this trial], Roxana Mehran, MD, professor and director of interventional cardiovascular research at Mount Sinai Hospital in New York, said in a video interview at the annual meeting of the American College of Cardiology.

In SURTAVI, which used Medtronic’s self-expanding CoreValve and Evolut-R bioprostheses in 863 patients randomized to TAVR, 12.6% met the study’s primary endpoint – death from any cause or disabling stroke at 24 months – versus 14% of the 796 patients randomized to surgery, a statistically nonsignificant difference. Notably, the risk of any type of stroke at 30 days was statistically superior for TAVR, 3.4%, compared with 5.6% for surgical replacement.

“It’s tremendously important to see the change in how we’re going to be evaluating patients with aortic stenosis,” Dr. Mehran said.

[email protected]

Washington – Heart teams will have more options when making treatment decisions for patients with severe aortic stenosis who are at intermediate risk, now that the results of the SURTAVI (Surgical Replacement and Transcatheter Aortic Valve Implantation) trial have been presented.

Those results showed that transcatheter aortic valve replacement (TAVR) in patients with severe aortic stenosis at intermediate risk was not only noninferior to surgical replacement, “but in my mind superior, because you don’t get your chest cracked, you get home earlier, and you have fewer strokes [in this trial], Roxana Mehran, MD, professor and director of interventional cardiovascular research at Mount Sinai Hospital in New York, said in a video interview at the annual meeting of the American College of Cardiology.

In SURTAVI, which used Medtronic’s self-expanding CoreValve and Evolut-R bioprostheses in 863 patients randomized to TAVR, 12.6% met the study’s primary endpoint – death from any cause or disabling stroke at 24 months – versus 14% of the 796 patients randomized to surgery, a statistically nonsignificant difference. Notably, the risk of any type of stroke at 30 days was statistically superior for TAVR, 3.4%, compared with 5.6% for surgical replacement.

“It’s tremendously important to see the change in how we’re going to be evaluating patients with aortic stenosis,” Dr. Mehran said.

[email protected]

WASHINGTON – With the results of two blockbuster trials in lipid-lowering PCSK9 inhibitors, the long-awaited verdict on LDL cholesterol’s effect on cardiovascular outcomes is in: Lower is better.

In a video interview at the annual meeting of the American College of Cardiology, Paul M. Ridker, MD, added that “lower is better for longer.”

Dr. Ridker presented results of the SPIRE (Studies of PCSK9 Inhibition and the Reduction of Vascular Events) program in bococizumab. Bococizumab was revealed to spur antibody responses in some patients, leading Pfizer to discontinue the SPIRE program and any further development. However, the combined endpoint for all six SPIRE trials was reduced by 25%, a trend that continued with longer treatment.

The FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) trial, presented by Marc S. Sabatine, MD, of Brigham and Women’s Hospital in Boston, showed a reduction of 15% in the cardiovascular events.

Both the SPIRE and the FOURIER program have now provided evidence saying “lower is better for longer,” Dr. Ridker said in a video interview. The challenge is, “who do we want to get these drugs into first?”

For his part, Dr. Ridker, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston, will focus on his very-high-risk patients who are receiving the most aggressive therapy possible. 

WASHINGTON – With the results of two blockbuster trials in lipid-lowering PCSK9 inhibitors, the long-awaited verdict on LDL cholesterol’s effect on cardiovascular outcomes is in: Lower is better.

In a video interview at the annual meeting of the American College of Cardiology, Paul M. Ridker, MD, added that “lower is better for longer.”

Dr. Ridker presented results of the SPIRE (Studies of PCSK9 Inhibition and the Reduction of Vascular Events) program in bococizumab. Bococizumab was revealed to spur antibody responses in some patients, leading Pfizer to discontinue the SPIRE program and any further development. However, the combined endpoint for all six SPIRE trials was reduced by 25%, a trend that continued with longer treatment.

The FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) trial, presented by Marc S. Sabatine, MD, of Brigham and Women’s Hospital in Boston, showed a reduction of 15% in the cardiovascular events.

Both the SPIRE and the FOURIER program have now provided evidence saying “lower is better for longer,” Dr. Ridker said in a video interview. The challenge is, “who do we want to get these drugs into first?”

For his part, Dr. Ridker, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston, will focus on his very-high-risk patients who are receiving the most aggressive therapy possible. 

WASHINGTON – With the results of two blockbuster trials in lipid-lowering PCSK9 inhibitors, the long-awaited verdict on LDL cholesterol’s effect on cardiovascular outcomes is in: Lower is better.

In a video interview at the annual meeting of the American College of Cardiology, Paul M. Ridker, MD, added that “lower is better for longer.”

Dr. Ridker presented results of the SPIRE (Studies of PCSK9 Inhibition and the Reduction of Vascular Events) program in bococizumab. Bococizumab was revealed to spur antibody responses in some patients, leading Pfizer to discontinue the SPIRE program and any further development. However, the combined endpoint for all six SPIRE trials was reduced by 25%, a trend that continued with longer treatment.

The FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) trial, presented by Marc S. Sabatine, MD, of Brigham and Women’s Hospital in Boston, showed a reduction of 15% in the cardiovascular events.

Both the SPIRE and the FOURIER program have now provided evidence saying “lower is better for longer,” Dr. Ridker said in a video interview. The challenge is, “who do we want to get these drugs into first?”

For his part, Dr. Ridker, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston, will focus on his very-high-risk patients who are receiving the most aggressive therapy possible. 

The small interfering RNA molecule inclisiran has achieved significant reductions in LDL-cholesterol levels in patients at high cardiovascular risk, according to data presented at the annual meeting of the American College of Cardiology and published simultaneously in the New England Journal of Medicine.

Inclisiran is an investigational, chemically synthesized, small interfering RNA molecule that targets the liver-derived serine protease proprotein convertase subtilisin-kexin type 9 (PCSK9), which promotes degradation of the LDL-receptor.

An earlier phase I trial of inclisiran in healthy volunteers showed sustained reductions in LDL-C levels. In this phase II randomized, placebo-controlled trial, researchers tested a single dose (200, 300, or 500 mg) or double dose (100, 200, or 300 mg on day 1 and day 90) subcutaneous injection, compared with placebo in 501 patients with elevated LDL-C who were at high risk for cardiovascular disease.

By day 30 after the first injection, mean reductions in LDL-C ranged from 44.5% to 50.5% below baseline levels across all dosages of inclisiran (N Engl J Med. 2017 Mar 17. doi: 10.1056/NEJMoa1615758).

By day 180, the mean reductions in LDL-C were 27.9%-41.9% in patients who received a single dose and 35.5%-52.6% in those who received a double dose. By comparison, patients who received placebo showed a 2.1% mean increase in LDL-C.

All patients who received two 300-mg doses of inclisiran showed reductions in LDL-C by day 180, with a mean absolute change of –64.2 ± 20.7 mg/dL. More than half of this group (54%) achieved LDL-C reductions of 50% or more below baseline.

In this same dosage group, 5% of patients achieved LDL-C levels below 25 mg/dL, 48% achieved levels below 50 mg/dL, and 66% achieved levels below 70 mg/dL by day 180 after the first dose.

Researchers observed a nadir in patients’ response at around day 60 for the single-dose group and day 140 for the double-dose group.

“Maintaining consistent and effective reductions in LDL-cholesterol levels in the long term through the use of statins is, in part, hindered by adherence,” wrote Kausik K. Ray, MD, of Imperial College London, and his coauthors. “Hence, approaches that not only lower LDL-cholesterol levels safely but also can maintain reduction consistently over time, when applied either in lieu of or simultaneously with statin therapy, are being sought.”

However, they also clarified that it was still unknown as to whether these LDL-C reductions would translate into reductions in cardiovascular events.

Researchers also saw significant declines in PCSK9 levels from baseline in all patients who received inclisiran. Among those who received a single dose, mean reductions in PCSK9 at 180 days ranged from 47.9% to 59.3%, while those who received a double dose showed mean reductions ranging from 53.2% to 69.1%.

The overall rate of adverse events was similar between the inclisiran and placebo groups (76% vs. 79%, respectively), while the rate of serious adverse events was 11% in the inclisiran group and 8% in the placebo group.

One patient in the inclisiran group and one in the placebo group showed increased levels of hepatic aspartate aminotransferase, and three patients in the inclisiran group had elevated alanine aminotransferase. No increases in bilirubin levels were observed.

“Symptoms of immune activation, which is often a concern with therapies targeting RNA, were rare in association with inclisiran: There were few instances of flu-like symptoms and no observed elevations in C-reactive protein,” the authors wrote.

Injection-site reactions were also relatively uncommon, occurring in 4% of patients treated with one dose of inclisiran, 7% of those treated with two doses, and none of the placebo group.

The authors, however, said that, given the small size and relatively short duration of the trial, they could not rule out the possibility of other infrequent serious side effects. A long-term open-label study also is being conducted.

The study was funded by the Medicines Company. Several authors declared receiving personal fees from pharmaceutical companies outside the submitted work and 10 also declared receiving personal fees from the Medicines Company, 6 involving the submitted work. One author was an employee of the Medicines Company with stock options.

The small interfering RNA molecule inclisiran has achieved significant reductions in LDL-cholesterol levels in patients at high cardiovascular risk, according to data presented at the annual meeting of the American College of Cardiology and published simultaneously in the New England Journal of Medicine.

Inclisiran is an investigational, chemically synthesized, small interfering RNA molecule that targets the liver-derived serine protease proprotein convertase subtilisin-kexin type 9 (PCSK9), which promotes degradation of the LDL-receptor.

An earlier phase I trial of inclisiran in healthy volunteers showed sustained reductions in LDL-C levels. In this phase II randomized, placebo-controlled trial, researchers tested a single dose (200, 300, or 500 mg) or double dose (100, 200, or 300 mg on day 1 and day 90) subcutaneous injection, compared with placebo in 501 patients with elevated LDL-C who were at high risk for cardiovascular disease.

By day 30 after the first injection, mean reductions in LDL-C ranged from 44.5% to 50.5% below baseline levels across all dosages of inclisiran (N Engl J Med. 2017 Mar 17. doi: 10.1056/NEJMoa1615758).

By day 180, the mean reductions in LDL-C were 27.9%-41.9% in patients who received a single dose and 35.5%-52.6% in those who received a double dose. By comparison, patients who received placebo showed a 2.1% mean increase in LDL-C.

All patients who received two 300-mg doses of inclisiran showed reductions in LDL-C by day 180, with a mean absolute change of –64.2 ± 20.7 mg/dL. More than half of this group (54%) achieved LDL-C reductions of 50% or more below baseline.

In this same dosage group, 5% of patients achieved LDL-C levels below 25 mg/dL, 48% achieved levels below 50 mg/dL, and 66% achieved levels below 70 mg/dL by day 180 after the first dose.

Researchers observed a nadir in patients’ response at around day 60 for the single-dose group and day 140 for the double-dose group.

“Maintaining consistent and effective reductions in LDL-cholesterol levels in the long term through the use of statins is, in part, hindered by adherence,” wrote Kausik K. Ray, MD, of Imperial College London, and his coauthors. “Hence, approaches that not only lower LDL-cholesterol levels safely but also can maintain reduction consistently over time, when applied either in lieu of or simultaneously with statin therapy, are being sought.”

However, they also clarified that it was still unknown as to whether these LDL-C reductions would translate into reductions in cardiovascular events.

Researchers also saw significant declines in PCSK9 levels from baseline in all patients who received inclisiran. Among those who received a single dose, mean reductions in PCSK9 at 180 days ranged from 47.9% to 59.3%, while those who received a double dose showed mean reductions ranging from 53.2% to 69.1%.

The overall rate of adverse events was similar between the inclisiran and placebo groups (76% vs. 79%, respectively), while the rate of serious adverse events was 11% in the inclisiran group and 8% in the placebo group.

One patient in the inclisiran group and one in the placebo group showed increased levels of hepatic aspartate aminotransferase, and three patients in the inclisiran group had elevated alanine aminotransferase. No increases in bilirubin levels were observed.

“Symptoms of immune activation, which is often a concern with therapies targeting RNA, were rare in association with inclisiran: There were few instances of flu-like symptoms and no observed elevations in C-reactive protein,” the authors wrote.

Injection-site reactions were also relatively uncommon, occurring in 4% of patients treated with one dose of inclisiran, 7% of those treated with two doses, and none of the placebo group.

The authors, however, said that, given the small size and relatively short duration of the trial, they could not rule out the possibility of other infrequent serious side effects. A long-term open-label study also is being conducted.

The study was funded by the Medicines Company. Several authors declared receiving personal fees from pharmaceutical companies outside the submitted work and 10 also declared receiving personal fees from the Medicines Company, 6 involving the submitted work. One author was an employee of the Medicines Company with stock options.

The small interfering RNA molecule inclisiran has achieved significant reductions in LDL-cholesterol levels in patients at high cardiovascular risk, according to data presented at the annual meeting of the American College of Cardiology and published simultaneously in the New England Journal of Medicine.

Inclisiran is an investigational, chemically synthesized, small interfering RNA molecule that targets the liver-derived serine protease proprotein convertase subtilisin-kexin type 9 (PCSK9), which promotes degradation of the LDL-receptor.

An earlier phase I trial of inclisiran in healthy volunteers showed sustained reductions in LDL-C levels. In this phase II randomized, placebo-controlled trial, researchers tested a single dose (200, 300, or 500 mg) or double dose (100, 200, or 300 mg on day 1 and day 90) subcutaneous injection, compared with placebo in 501 patients with elevated LDL-C who were at high risk for cardiovascular disease.

By day 30 after the first injection, mean reductions in LDL-C ranged from 44.5% to 50.5% below baseline levels across all dosages of inclisiran (N Engl J Med. 2017 Mar 17. doi: 10.1056/NEJMoa1615758).

By day 180, the mean reductions in LDL-C were 27.9%-41.9% in patients who received a single dose and 35.5%-52.6% in those who received a double dose. By comparison, patients who received placebo showed a 2.1% mean increase in LDL-C.

All patients who received two 300-mg doses of inclisiran showed reductions in LDL-C by day 180, with a mean absolute change of –64.2 ± 20.7 mg/dL. More than half of this group (54%) achieved LDL-C reductions of 50% or more below baseline.

In this same dosage group, 5% of patients achieved LDL-C levels below 25 mg/dL, 48% achieved levels below 50 mg/dL, and 66% achieved levels below 70 mg/dL by day 180 after the first dose.

Researchers observed a nadir in patients’ response at around day 60 for the single-dose group and day 140 for the double-dose group.

“Maintaining consistent and effective reductions in LDL-cholesterol levels in the long term through the use of statins is, in part, hindered by adherence,” wrote Kausik K. Ray, MD, of Imperial College London, and his coauthors. “Hence, approaches that not only lower LDL-cholesterol levels safely but also can maintain reduction consistently over time, when applied either in lieu of or simultaneously with statin therapy, are being sought.”

However, they also clarified that it was still unknown as to whether these LDL-C reductions would translate into reductions in cardiovascular events.

Researchers also saw significant declines in PCSK9 levels from baseline in all patients who received inclisiran. Among those who received a single dose, mean reductions in PCSK9 at 180 days ranged from 47.9% to 59.3%, while those who received a double dose showed mean reductions ranging from 53.2% to 69.1%.

The overall rate of adverse events was similar between the inclisiran and placebo groups (76% vs. 79%, respectively), while the rate of serious adverse events was 11% in the inclisiran group and 8% in the placebo group.

One patient in the inclisiran group and one in the placebo group showed increased levels of hepatic aspartate aminotransferase, and three patients in the inclisiran group had elevated alanine aminotransferase. No increases in bilirubin levels were observed.

“Symptoms of immune activation, which is often a concern with therapies targeting RNA, were rare in association with inclisiran: There were few instances of flu-like symptoms and no observed elevations in C-reactive protein,” the authors wrote.

Injection-site reactions were also relatively uncommon, occurring in 4% of patients treated with one dose of inclisiran, 7% of those treated with two doses, and none of the placebo group.

The authors, however, said that, given the small size and relatively short duration of the trial, they could not rule out the possibility of other infrequent serious side effects. A long-term open-label study also is being conducted.

The study was funded by the Medicines Company. Several authors declared receiving personal fees from pharmaceutical companies outside the submitted work and 10 also declared receiving personal fees from the Medicines Company, 6 involving the submitted work. One author was an employee of the Medicines Company with stock options.