New cholesterol guidelines would add 13 million new statin users

Strict adherence to the new risk-based American College of Cardiology–American Heart Association guidelines for managing cholesterol would increase the number of adults eligible for statin therapy by nearly 13 million, a study suggests.

Most of the increase would be among older adults without cardiovascular disease, Michael J. Pencina, Ph.D., of the Duke Clinical Research Institute of Duke University, Durham, N.C., and his colleagues reported online March 19 in the New England Journal of Medicine.

The investigators used fasting data from 3,773 adults aged 40-75 years who participated in the National Health and Nutrition Examination Survey (NHANES) of 2005-2010 to estimate the number of individuals for whom statin therapy would be recommended under the new guidelines, published in November 2013, compared with the previously recommended 2007 guidelines from the Third Adult Treatment Panel (ATP III) of the National Cholesterol Education Program.

After extrapolating the results to the estimated population of U.S. adults aged 40-75 years (115.4 million adults), they determined that 14.4 million adults would be newly eligible for statin therapy based on the new guidelines, and that 1.6 million previously eligible adults would become ineligible under the new guidelines, for a net increase in the number of adults receiving or eligible for statin therapy from 43.2 million (38%) to 56.0 million (49%), the investigators said (N. Engl. J. Med. 2014 March 19 [doi: 10.1056/NEJMoa1315665]).

Of the 12.8 million additional eligible adults, 10.4 million would be individuals without existing cardiovascular disease, and 8.4 million of those would be aged 60-75 years; among the 60- to 75-year-olds without cardiovascular disease, the percentage eligible would increase from 30% to 87% for men, and from 21% to 54% for women.

"The median age of adults who would be newly eligible for statin therapy under the new ACC-AHA guidelines would be 63.4 years, and 61.7% would be men. The median LDL cholesterol level for these adults is 105.2 mg per deciliter," the investigators wrote, adding that the new guidelines increase the estimated number of adults who would be eligible across all categories.

The largest increase would occur among adults who have an indication for primary prevention on the basis of their 10-year risk of cardiovascular disease (15.1 million by the new guidelines vs. 6.9 million by ATP III), they said.

"Furthermore, 2.4 million adults with prevalent cardiovascular disease and LDL cholesterol levels of less than 100 mg per deciliter who would not be eligible for statin therapy according to the ATP III guidelines would be eligible under the new ACC-AHA guidelines. Finally, the number of adults with diabetes who are eligible for statin therapy would increase from 4.5 million to 6.7 million as a result of the lowering of the threshold for LDL cholesterol treatment from 100 to 70 mg per deciliter," the investigators wrote.

According to the ATP III guidelines, patients with established cardiovascular disease or diabetes and LDL cholesterol levels of 100 mg/dL or higher were eligible for statin therapy. Those guidelines also recommended statins for primary prevention in patients on the basis of a combined assessment of LDL cholesterol and a 10-year risk of coronary heart disease.

The new ACC-AHA guidelines differ substantially from the ATP III guidelines in that they expand the treatment recommendation to all adults with known cardiovascular disease, regardless of LDL cholesterol level, and for primary prevention they recommend statin therapy for all those with an LDL cholesterol level of 70 mg/dL or higher and who also have diabetes or a 10-year risk of cardiovascular disease of 7.5% or greater based on new pooled-cohort equations.

"These new treatment recommendations have a larger effect in the older age group (60 to 75 years) than in the younger age group (40 to 59 years). Although up to 30% of adults in the younger age group without cardiovascular disease would be eligible for statin therapy for primary prevention, more than 77% of those in the older age group would be eligible. This difference might be partially explained by the addition of stroke to coronary heart disease as a target for prevention in the new pooled-cohort equations," they wrote. Because the prevalence of cardiovascular disease rises markedly with age, the large proportion of older adults who would be eligible for statin therapy may be justifiable, they added.

"Further research is required to determine whether more aggressive preventive strategies are needed for younger adults," they said.

Though limited by a number of factors, such as the extrapolation of data from 3,773 NHANES participants to 115.4 million U.S. adults, and by an inability to accurately quantify the effects of the new and old guidelines on patients currently receiving lipid-lowering therapy (since it was unclear why therapy was initiated), the findings nonetheless suggest a need for personalization with respect to applying the new guidelines.

The new guidelines "treat risk as the predominant reason for treating patients," according to one of the study’s lead authors, Dr. Eric D. Peterson of Duke University.

However, there is a paucity of data on the whether this approach works for older adults, Dr. Peterson said in an interview.

"I’m not willing to say we will be overtreating these patients [based on the new guidelines], but we need more data; this is a pretty big leap," he said.

Conversely, the new guidelines could lead to undertreatment of younger patients with high lipid levels, he added.

"This is kind of frightening," Dr. Peterson said, explaining that a younger patient who appears to have a relatively low 10-year risk of developing cardiovascular disease, but who has high lipid levels, would not be recommended for intervention – even though such a patient has a high likelihood of eventually developing cardiovascular disease.

"There is good research saying we should treat these patients, but these guidelines don’t recommend that. If we strictly follow the guidelines, we will undertreat younger patients," he said.

It is important to remember that the new guidelines are not "the letter of law," but rather are guides.

"Some degree of personalization for the patient in front of us is definitely needed right now," he said.

Dr. Donald M. Lloyd-Jones, cochair of the ACC-AHA guidelines, said he "agrees with the careful analysis" by Dr. Pencina, Dr. Peterson, and their colleagues.

"These findings are consistent with the analyses we reported in the guideline documents using NHANES data," said Dr. Lloyd-Jones, senior associate dean and professor and chair of preventive medicine at Northwestern University Feinberg School of Medicine, Chicago.

Of note, the majority of the difference between the estimates based on the ATP III guidelines and the ACC-AHA guidelines is due to the lower threshold for consideration of treatment, which was derived directly from the evidence base from newer primary-prevention randomized clinical trials, he said.

"The authors recognized that the reported estimate is the maximum estimate of the increase in the number of people potentially eligible for statin therapy, because the guideline recommendation is for the clinician and patient to use the risk equations as the starting point for a risk discussion, not to mandate a statin prescription," he said.

Additionally, the results "refute the alarmist claims that we saw from a number of commentators in the media a few months ago that 70-100 million Americans would be put on statin therapy as a result of the new guidelines," Dr. Lloyd-Jones said.

"With one in three Americans dying of a preventable or postponable cardiovascular event, and more than half experiencing a major vascular event before they die, evidence-based guidelines that recommend that statins be considered for about half of American adults seem about right. Furthermore, we currently recommend that about 70 million Americans be treated for hypertension, so recommending that about 50 million should be considered for statins also seems about right," he said.

This study was funded by the Duke Clinical Research Institute and by grants from M. Jean de Granpre and Louis and Sylvia Vogel. Dr. Pencina reported receiving research fees (unrelated to this study) from McGill University Health Center and AbbVie. Dr. Peterson reported receiving grants from Eli Lilly and grant support and/or personal fees from Janssen and Boehringer Ingelheim. The remaining authors reported having nothing to disclose.

Strict adherence to the new risk-based American College of Cardiology–American Heart Association guidelines for managing cholesterol would increase the number of adults eligible for statin therapy by nearly 13 million, a study suggests.

Most of the increase would be among older adults without cardiovascular disease, Michael J. Pencina, Ph.D., of the Duke Clinical Research Institute of Duke University, Durham, N.C., and his colleagues reported online March 19 in the New England Journal of Medicine.

The investigators used fasting data from 3,773 adults aged 40-75 years who participated in the National Health and Nutrition Examination Survey (NHANES) of 2005-2010 to estimate the number of individuals for whom statin therapy would be recommended under the new guidelines, published in November 2013, compared with the previously recommended 2007 guidelines from the Third Adult Treatment Panel (ATP III) of the National Cholesterol Education Program.

After extrapolating the results to the estimated population of U.S. adults aged 40-75 years (115.4 million adults), they determined that 14.4 million adults would be newly eligible for statin therapy based on the new guidelines, and that 1.6 million previously eligible adults would become ineligible under the new guidelines, for a net increase in the number of adults receiving or eligible for statin therapy from 43.2 million (38%) to 56.0 million (49%), the investigators said (N. Engl. J. Med. 2014 March 19 [doi: 10.1056/NEJMoa1315665]).

Of the 12.8 million additional eligible adults, 10.4 million would be individuals without existing cardiovascular disease, and 8.4 million of those would be aged 60-75 years; among the 60- to 75-year-olds without cardiovascular disease, the percentage eligible would increase from 30% to 87% for men, and from 21% to 54% for women.

"The median age of adults who would be newly eligible for statin therapy under the new ACC-AHA guidelines would be 63.4 years, and 61.7% would be men. The median LDL cholesterol level for these adults is 105.2 mg per deciliter," the investigators wrote, adding that the new guidelines increase the estimated number of adults who would be eligible across all categories.

The largest increase would occur among adults who have an indication for primary prevention on the basis of their 10-year risk of cardiovascular disease (15.1 million by the new guidelines vs. 6.9 million by ATP III), they said.

"Furthermore, 2.4 million adults with prevalent cardiovascular disease and LDL cholesterol levels of less than 100 mg per deciliter who would not be eligible for statin therapy according to the ATP III guidelines would be eligible under the new ACC-AHA guidelines. Finally, the number of adults with diabetes who are eligible for statin therapy would increase from 4.5 million to 6.7 million as a result of the lowering of the threshold for LDL cholesterol treatment from 100 to 70 mg per deciliter," the investigators wrote.

According to the ATP III guidelines, patients with established cardiovascular disease or diabetes and LDL cholesterol levels of 100 mg/dL or higher were eligible for statin therapy. Those guidelines also recommended statins for primary prevention in patients on the basis of a combined assessment of LDL cholesterol and a 10-year risk of coronary heart disease.

The new ACC-AHA guidelines differ substantially from the ATP III guidelines in that they expand the treatment recommendation to all adults with known cardiovascular disease, regardless of LDL cholesterol level, and for primary prevention they recommend statin therapy for all those with an LDL cholesterol level of 70 mg/dL or higher and who also have diabetes or a 10-year risk of cardiovascular disease of 7.5% or greater based on new pooled-cohort equations.

"These new treatment recommendations have a larger effect in the older age group (60 to 75 years) than in the younger age group (40 to 59 years). Although up to 30% of adults in the younger age group without cardiovascular disease would be eligible for statin therapy for primary prevention, more than 77% of those in the older age group would be eligible. This difference might be partially explained by the addition of stroke to coronary heart disease as a target for prevention in the new pooled-cohort equations," they wrote. Because the prevalence of cardiovascular disease rises markedly with age, the large proportion of older adults who would be eligible for statin therapy may be justifiable, they added.

"Further research is required to determine whether more aggressive preventive strategies are needed for younger adults," they said.

Though limited by a number of factors, such as the extrapolation of data from 3,773 NHANES participants to 115.4 million U.S. adults, and by an inability to accurately quantify the effects of the new and old guidelines on patients currently receiving lipid-lowering therapy (since it was unclear why therapy was initiated), the findings nonetheless suggest a need for personalization with respect to applying the new guidelines.

The new guidelines "treat risk as the predominant reason for treating patients," according to one of the study’s lead authors, Dr. Eric D. Peterson of Duke University.

However, there is a paucity of data on the whether this approach works for older adults, Dr. Peterson said in an interview.

"I’m not willing to say we will be overtreating these patients [based on the new guidelines], but we need more data; this is a pretty big leap," he said.

Conversely, the new guidelines could lead to undertreatment of younger patients with high lipid levels, he added.

"This is kind of frightening," Dr. Peterson said, explaining that a younger patient who appears to have a relatively low 10-year risk of developing cardiovascular disease, but who has high lipid levels, would not be recommended for intervention – even though such a patient has a high likelihood of eventually developing cardiovascular disease.

"There is good research saying we should treat these patients, but these guidelines don’t recommend that. If we strictly follow the guidelines, we will undertreat younger patients," he said.

It is important to remember that the new guidelines are not "the letter of law," but rather are guides.

"Some degree of personalization for the patient in front of us is definitely needed right now," he said.

Dr. Donald M. Lloyd-Jones, cochair of the ACC-AHA guidelines, said he "agrees with the careful analysis" by Dr. Pencina, Dr. Peterson, and their colleagues.

"These findings are consistent with the analyses we reported in the guideline documents using NHANES data," said Dr. Lloyd-Jones, senior associate dean and professor and chair of preventive medicine at Northwestern University Feinberg School of Medicine, Chicago.

Of note, the majority of the difference between the estimates based on the ATP III guidelines and the ACC-AHA guidelines is due to the lower threshold for consideration of treatment, which was derived directly from the evidence base from newer primary-prevention randomized clinical trials, he said.

"The authors recognized that the reported estimate is the maximum estimate of the increase in the number of people potentially eligible for statin therapy, because the guideline recommendation is for the clinician and patient to use the risk equations as the starting point for a risk discussion, not to mandate a statin prescription," he said.

Additionally, the results "refute the alarmist claims that we saw from a number of commentators in the media a few months ago that 70-100 million Americans would be put on statin therapy as a result of the new guidelines," Dr. Lloyd-Jones said.

"With one in three Americans dying of a preventable or postponable cardiovascular event, and more than half experiencing a major vascular event before they die, evidence-based guidelines that recommend that statins be considered for about half of American adults seem about right. Furthermore, we currently recommend that about 70 million Americans be treated for hypertension, so recommending that about 50 million should be considered for statins also seems about right," he said.

This study was funded by the Duke Clinical Research Institute and by grants from M. Jean de Granpre and Louis and Sylvia Vogel. Dr. Pencina reported receiving research fees (unrelated to this study) from McGill University Health Center and AbbVie. Dr. Peterson reported receiving grants from Eli Lilly and grant support and/or personal fees from Janssen and Boehringer Ingelheim. The remaining authors reported having nothing to disclose.

Strict adherence to the new risk-based American College of Cardiology–American Heart Association guidelines for managing cholesterol would increase the number of adults eligible for statin therapy by nearly 13 million, a study suggests.

Most of the increase would be among older adults without cardiovascular disease, Michael J. Pencina, Ph.D., of the Duke Clinical Research Institute of Duke University, Durham, N.C., and his colleagues reported online March 19 in the New England Journal of Medicine.

The investigators used fasting data from 3,773 adults aged 40-75 years who participated in the National Health and Nutrition Examination Survey (NHANES) of 2005-2010 to estimate the number of individuals for whom statin therapy would be recommended under the new guidelines, published in November 2013, compared with the previously recommended 2007 guidelines from the Third Adult Treatment Panel (ATP III) of the National Cholesterol Education Program.

After extrapolating the results to the estimated population of U.S. adults aged 40-75 years (115.4 million adults), they determined that 14.4 million adults would be newly eligible for statin therapy based on the new guidelines, and that 1.6 million previously eligible adults would become ineligible under the new guidelines, for a net increase in the number of adults receiving or eligible for statin therapy from 43.2 million (38%) to 56.0 million (49%), the investigators said (N. Engl. J. Med. 2014 March 19 [doi: 10.1056/NEJMoa1315665]).

Of the 12.8 million additional eligible adults, 10.4 million would be individuals without existing cardiovascular disease, and 8.4 million of those would be aged 60-75 years; among the 60- to 75-year-olds without cardiovascular disease, the percentage eligible would increase from 30% to 87% for men, and from 21% to 54% for women.

"The median age of adults who would be newly eligible for statin therapy under the new ACC-AHA guidelines would be 63.4 years, and 61.7% would be men. The median LDL cholesterol level for these adults is 105.2 mg per deciliter," the investigators wrote, adding that the new guidelines increase the estimated number of adults who would be eligible across all categories.

The largest increase would occur among adults who have an indication for primary prevention on the basis of their 10-year risk of cardiovascular disease (15.1 million by the new guidelines vs. 6.9 million by ATP III), they said.

"Furthermore, 2.4 million adults with prevalent cardiovascular disease and LDL cholesterol levels of less than 100 mg per deciliter who would not be eligible for statin therapy according to the ATP III guidelines would be eligible under the new ACC-AHA guidelines. Finally, the number of adults with diabetes who are eligible for statin therapy would increase from 4.5 million to 6.7 million as a result of the lowering of the threshold for LDL cholesterol treatment from 100 to 70 mg per deciliter," the investigators wrote.

According to the ATP III guidelines, patients with established cardiovascular disease or diabetes and LDL cholesterol levels of 100 mg/dL or higher were eligible for statin therapy. Those guidelines also recommended statins for primary prevention in patients on the basis of a combined assessment of LDL cholesterol and a 10-year risk of coronary heart disease.

The new ACC-AHA guidelines differ substantially from the ATP III guidelines in that they expand the treatment recommendation to all adults with known cardiovascular disease, regardless of LDL cholesterol level, and for primary prevention they recommend statin therapy for all those with an LDL cholesterol level of 70 mg/dL or higher and who also have diabetes or a 10-year risk of cardiovascular disease of 7.5% or greater based on new pooled-cohort equations.

"These new treatment recommendations have a larger effect in the older age group (60 to 75 years) than in the younger age group (40 to 59 years). Although up to 30% of adults in the younger age group without cardiovascular disease would be eligible for statin therapy for primary prevention, more than 77% of those in the older age group would be eligible. This difference might be partially explained by the addition of stroke to coronary heart disease as a target for prevention in the new pooled-cohort equations," they wrote. Because the prevalence of cardiovascular disease rises markedly with age, the large proportion of older adults who would be eligible for statin therapy may be justifiable, they added.

"Further research is required to determine whether more aggressive preventive strategies are needed for younger adults," they said.

Though limited by a number of factors, such as the extrapolation of data from 3,773 NHANES participants to 115.4 million U.S. adults, and by an inability to accurately quantify the effects of the new and old guidelines on patients currently receiving lipid-lowering therapy (since it was unclear why therapy was initiated), the findings nonetheless suggest a need for personalization with respect to applying the new guidelines.

The new guidelines "treat risk as the predominant reason for treating patients," according to one of the study’s lead authors, Dr. Eric D. Peterson of Duke University.

However, there is a paucity of data on the whether this approach works for older adults, Dr. Peterson said in an interview.

"I’m not willing to say we will be overtreating these patients [based on the new guidelines], but we need more data; this is a pretty big leap," he said.

Conversely, the new guidelines could lead to undertreatment of younger patients with high lipid levels, he added.

"This is kind of frightening," Dr. Peterson said, explaining that a younger patient who appears to have a relatively low 10-year risk of developing cardiovascular disease, but who has high lipid levels, would not be recommended for intervention – even though such a patient has a high likelihood of eventually developing cardiovascular disease.

"There is good research saying we should treat these patients, but these guidelines don’t recommend that. If we strictly follow the guidelines, we will undertreat younger patients," he said.

It is important to remember that the new guidelines are not "the letter of law," but rather are guides.

"Some degree of personalization for the patient in front of us is definitely needed right now," he said.

Dr. Donald M. Lloyd-Jones, cochair of the ACC-AHA guidelines, said he "agrees with the careful analysis" by Dr. Pencina, Dr. Peterson, and their colleagues.

"These findings are consistent with the analyses we reported in the guideline documents using NHANES data," said Dr. Lloyd-Jones, senior associate dean and professor and chair of preventive medicine at Northwestern University Feinberg School of Medicine, Chicago.

Of note, the majority of the difference between the estimates based on the ATP III guidelines and the ACC-AHA guidelines is due to the lower threshold for consideration of treatment, which was derived directly from the evidence base from newer primary-prevention randomized clinical trials, he said.

"The authors recognized that the reported estimate is the maximum estimate of the increase in the number of people potentially eligible for statin therapy, because the guideline recommendation is for the clinician and patient to use the risk equations as the starting point for a risk discussion, not to mandate a statin prescription," he said.

Additionally, the results "refute the alarmist claims that we saw from a number of commentators in the media a few months ago that 70-100 million Americans would be put on statin therapy as a result of the new guidelines," Dr. Lloyd-Jones said.

"With one in three Americans dying of a preventable or postponable cardiovascular event, and more than half experiencing a major vascular event before they die, evidence-based guidelines that recommend that statins be considered for about half of American adults seem about right. Furthermore, we currently recommend that about 70 million Americans be treated for hypertension, so recommending that about 50 million should be considered for statins also seems about right," he said.

This study was funded by the Duke Clinical Research Institute and by grants from M. Jean de Granpre and Louis and Sylvia Vogel. Dr. Pencina reported receiving research fees (unrelated to this study) from McGill University Health Center and AbbVie. Dr. Peterson reported receiving grants from Eli Lilly and grant support and/or personal fees from Janssen and Boehringer Ingelheim. The remaining authors reported having nothing to disclose.