New Cholesterol Guidelines Would Significantly Increase Statin Use If Implemented

Pencina MJ, Navar-Boggan AM, D’Agostino RB, et al. Application of new cholesterol guidelines to a population-based sample. N Engl J Med 2014;370:1422–31.
 

Study Overview

Objective. To quantify how many people would qualify for statin treatment under the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines [1].

Design. Descriptive, repeated cross-sectional study examining data from the 2005–2010 National Health and Nutrition Examination Surveys (NHANES). Data on the medical diagnoses and risk factors for cardiovascular disease for NHANES participants aged 40–75 years (n = 3773) were used to extrapolate to 115.4 million US adults in the same age-range. Exclusions were for triglyceride levels > 400 mg/dL (100 participants) and missing LDL cholesterol measurement (36 participants).

Main outcome measure. Percentage of the US adult population that would be recommended statin therapy according to the 2013 ACC/AHA guidelines as compared with the 2004 guideline produced by the Third Adult Treatment Panel (ATP III) of the National Cholesterol Education Program [2,3].

Main results. Of the NHANES participants, 49% were male, 13% had cardiovascular disease, 46% had hypertension, 21% had diabetes, 21% were smokers, and 41% had obesity. Median age was 56 years (interquartile range [IQR], 41–73), median total cholesterol was 199 mg/dL (IQR, 138–272), median LDL cholesterol was 118 mg/dL (IQR, 64–182), and HDL cholesterol was 52 mg/dL (IQR, 33–86).

Overall, 2135 participants (57%) qualified for statin treatment according to the ACC/AHA guidelines as compared with 1583 (42%) under the ATP III guidelines. Additional participants qualifying under the ACC/AHA guideline were more likely to be male, older in age, have a lower LDL cholesterol, and without known cardiovascular disease, diabetes, obesity, or hypertension. Extrapolated to the US population, 56 million people (49% of the US population age 40 to 75 years, 95% CI, 46–51) would be recommended for statin treatment under the ACC/AHA guidelines compared with 43.2 million (37.5%, 95% CI, 35.3–39.7) under ATP III.

Most new candidates for statins meet criteria for primary prevention of a cardiovascular event: 2.2 million persons with diabetes and 8.2 million considered at high risk for an event in 10 years based on the new ACC/AHA risk calculator [4]. Age also was an important predictor of newly eligible statin candidates. According to ATP III, 48% of 60- to 75-year-olds would qualify for treatment, but 78% would qualify based on ACC/AHA. According to extrapolated NHANES data, 25.2 million people were taking statins from 2005 to 2010; the ACC/AHA guidelines would more than double this number.

Conclusion. The 2013 ACC/AHA cholesterol treatment guidelines would substantially increase the number of patients recommended for statin therapy.

Commentary

In November 2013, the long-awaited cholesterol treatment guidelines from the ACC/AHA hit like an earthquake [5]. The guidelines called for abandoning the traditional treat-to-target approach, in which clinicians treat patients to specific levels of LDL cholesterol [1] and instead called for statin treatment based on cardiovascular risk profile. The guideline authors made this change because of the lack of evidence supporting a treat-to-target approach; nearly all randomized controlled trials with statins used fixed doses of statins rather than trying to achieve specific LDL levels. This study by Pencina and colleagues demonstrates how implementation of the new guideline could dramatically change practice. If fully implemented, the guideline would lead to treatment for more than 12 million more patients and double the number of currently treated patients. Nearly all of the newly treated patients would receive treatment for primary prevention.

The guideline defines 4 categories of patients to be considered for treatment: (1) patients with known cardiovascular disease, (2) patients with LDL cholesterol ≥ 190 mg/dL, (3) patients with diabetes aged 40 to 75 years and LDL cholesterol ≥ 70 mg/dL, and (4) patients aged 40 to 75 years with LDL cholesterol ≥ 70 mg/dL and an estimated 10-year risk of a cardiovascular event of ≥ 7.5%. The guidelines call for patients in groups 1 and 2 to receive high-intensity statins (rosuvastatin 20 to 40 mg, atorvastatin 40 to 80 mg), although patients with known cardiovascular disease > 75 years of age can receive moderate-intensity statins. Group 3 should receive high-intensity statins if their 10-year risk is ≥ 7.5%; if otherwise, they can receive a moderate-intensity statin. Group 4 should receive a moderate-to high-intensity statin. As with most guidelines, the guidelines offer the caveat that physicians should take an informed consent approach regarding treatment and make decisions in consultation with their patients.

The publicity surrounding the new guidelines was heightened by the controversy that emerged regarding the new Pooled Cohort Risk Equation developed by the guideline committee [4] for determining 10-year risk. Using data from 5 well-known cohort studies (over 24,000 participants), they created the new risk calculator because of what they viewed as limitations of existing risk calculators: (1) the lack of racial diversity in samples used to derive them, (2) the lack of use of stroke as a cardiovascular outcome, and (3) the use of some subjective outcomes, such as coronary revascularization, angina, and congestive heart failure. Critics have suggested that the new risk calculator is poorly calibrated to more recent cohorts and that the threshold for treatment (≥ 7.5% 10-year risk) is too low and should be 10% or higher [6,7].

Physicians have long used risk calculators to help guide treatment. As an example, the Framingham Heart Study risk score was endorsed by the ATP III guideline. However, all risk scores have limitations, as clearly articulated by the developers of the ACC/AHA risk calculator:

This process is admittedly imperfect; no one has 10% or 20% of a heart attack during a 10-year period. Individuals with the same estimated risk will either have or not have the event of interest, and only those patients who are destined to have an event can have their event prevented by therapy. The criticism of the risk estimation approach to treatment-decision making also applies to the alternative, and much less efficient approach, of checking the patient’s characteristics against numerous and complex inclusion and exclusion criteria for a potentially large number of pertinent trials [4].

No matter how well calibrated or thoughtful, all calculators will be flawed. But guidelines are meant to be just that—guides rather than a prescription for treatment.

Applications for Clinical Practice

The ACC and AHA have promised a 2014 update to their guideline, which may come with adjustments to the risk calculator. Perhaps calibration of the calculator in newer cohorts will improve and the threshold for treatment will change. In the meantime, the guidelines and the accompanying calculator have an important role in helping physicians decide whom to treat for primary prevention of cardiovascular disease. Physicians should consider applying the new guidelines, while having an informed consent discussion with their patients about the risks and benefits of treatment.

—Jason P. Block, MD, MPH

References

1. Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013 Nov 7 [Epub ahead of print].

2. Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. J Am Coll Cardiol 2004;44:720–32.

3. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002;106:3143–421.

4. Goff DC, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013 Nov 7 [Epub ahead of print].

5. Kolata G. Risk calculator for cholesterol appears flawed. New York Times. 17 November 2013. Accessed at www.nytimes.com/2013/11/18/health/risk-calculator-for-cholesterol-appears-flawed.html?_r_0 on 10 April 2014.

6. Ridker PM, Cook NR. Statins: new American guidelines for prevention of cardiovascular disease. Lancet 2013;382: 1762–5.

7. Downs J, Good C. New cholesterol guidelines: has Godot finally arrived? Ann Intern Med 2014;160:354–5.

Pencina MJ, Navar-Boggan AM, D’Agostino RB, et al. Application of new cholesterol guidelines to a population-based sample. N Engl J Med 2014;370:1422–31.
 

Study Overview

Objective. To quantify how many people would qualify for statin treatment under the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines [1].

Design. Descriptive, repeated cross-sectional study examining data from the 2005–2010 National Health and Nutrition Examination Surveys (NHANES). Data on the medical diagnoses and risk factors for cardiovascular disease for NHANES participants aged 40–75 years (n = 3773) were used to extrapolate to 115.4 million US adults in the same age-range. Exclusions were for triglyceride levels > 400 mg/dL (100 participants) and missing LDL cholesterol measurement (36 participants).

Main outcome measure. Percentage of the US adult population that would be recommended statin therapy according to the 2013 ACC/AHA guidelines as compared with the 2004 guideline produced by the Third Adult Treatment Panel (ATP III) of the National Cholesterol Education Program [2,3].

Main results. Of the NHANES participants, 49% were male, 13% had cardiovascular disease, 46% had hypertension, 21% had diabetes, 21% were smokers, and 41% had obesity. Median age was 56 years (interquartile range [IQR], 41–73), median total cholesterol was 199 mg/dL (IQR, 138–272), median LDL cholesterol was 118 mg/dL (IQR, 64–182), and HDL cholesterol was 52 mg/dL (IQR, 33–86).

Overall, 2135 participants (57%) qualified for statin treatment according to the ACC/AHA guidelines as compared with 1583 (42%) under the ATP III guidelines. Additional participants qualifying under the ACC/AHA guideline were more likely to be male, older in age, have a lower LDL cholesterol, and without known cardiovascular disease, diabetes, obesity, or hypertension. Extrapolated to the US population, 56 million people (49% of the US population age 40 to 75 years, 95% CI, 46–51) would be recommended for statin treatment under the ACC/AHA guidelines compared with 43.2 million (37.5%, 95% CI, 35.3–39.7) under ATP III.

Most new candidates for statins meet criteria for primary prevention of a cardiovascular event: 2.2 million persons with diabetes and 8.2 million considered at high risk for an event in 10 years based on the new ACC/AHA risk calculator [4]. Age also was an important predictor of newly eligible statin candidates. According to ATP III, 48% of 60- to 75-year-olds would qualify for treatment, but 78% would qualify based on ACC/AHA. According to extrapolated NHANES data, 25.2 million people were taking statins from 2005 to 2010; the ACC/AHA guidelines would more than double this number.

Conclusion. The 2013 ACC/AHA cholesterol treatment guidelines would substantially increase the number of patients recommended for statin therapy.

Commentary

In November 2013, the long-awaited cholesterol treatment guidelines from the ACC/AHA hit like an earthquake [5]. The guidelines called for abandoning the traditional treat-to-target approach, in which clinicians treat patients to specific levels of LDL cholesterol [1] and instead called for statin treatment based on cardiovascular risk profile. The guideline authors made this change because of the lack of evidence supporting a treat-to-target approach; nearly all randomized controlled trials with statins used fixed doses of statins rather than trying to achieve specific LDL levels. This study by Pencina and colleagues demonstrates how implementation of the new guideline could dramatically change practice. If fully implemented, the guideline would lead to treatment for more than 12 million more patients and double the number of currently treated patients. Nearly all of the newly treated patients would receive treatment for primary prevention.

The guideline defines 4 categories of patients to be considered for treatment: (1) patients with known cardiovascular disease, (2) patients with LDL cholesterol ≥ 190 mg/dL, (3) patients with diabetes aged 40 to 75 years and LDL cholesterol ≥ 70 mg/dL, and (4) patients aged 40 to 75 years with LDL cholesterol ≥ 70 mg/dL and an estimated 10-year risk of a cardiovascular event of ≥ 7.5%. The guidelines call for patients in groups 1 and 2 to receive high-intensity statins (rosuvastatin 20 to 40 mg, atorvastatin 40 to 80 mg), although patients with known cardiovascular disease > 75 years of age can receive moderate-intensity statins. Group 3 should receive high-intensity statins if their 10-year risk is ≥ 7.5%; if otherwise, they can receive a moderate-intensity statin. Group 4 should receive a moderate-to high-intensity statin. As with most guidelines, the guidelines offer the caveat that physicians should take an informed consent approach regarding treatment and make decisions in consultation with their patients.

The publicity surrounding the new guidelines was heightened by the controversy that emerged regarding the new Pooled Cohort Risk Equation developed by the guideline committee [4] for determining 10-year risk. Using data from 5 well-known cohort studies (over 24,000 participants), they created the new risk calculator because of what they viewed as limitations of existing risk calculators: (1) the lack of racial diversity in samples used to derive them, (2) the lack of use of stroke as a cardiovascular outcome, and (3) the use of some subjective outcomes, such as coronary revascularization, angina, and congestive heart failure. Critics have suggested that the new risk calculator is poorly calibrated to more recent cohorts and that the threshold for treatment (≥ 7.5% 10-year risk) is too low and should be 10% or higher [6,7].

Physicians have long used risk calculators to help guide treatment. As an example, the Framingham Heart Study risk score was endorsed by the ATP III guideline. However, all risk scores have limitations, as clearly articulated by the developers of the ACC/AHA risk calculator:

This process is admittedly imperfect; no one has 10% or 20% of a heart attack during a 10-year period. Individuals with the same estimated risk will either have or not have the event of interest, and only those patients who are destined to have an event can have their event prevented by therapy. The criticism of the risk estimation approach to treatment-decision making also applies to the alternative, and much less efficient approach, of checking the patient’s characteristics against numerous and complex inclusion and exclusion criteria for a potentially large number of pertinent trials [4].

No matter how well calibrated or thoughtful, all calculators will be flawed. But guidelines are meant to be just that—guides rather than a prescription for treatment.

Applications for Clinical Practice

The ACC and AHA have promised a 2014 update to their guideline, which may come with adjustments to the risk calculator. Perhaps calibration of the calculator in newer cohorts will improve and the threshold for treatment will change. In the meantime, the guidelines and the accompanying calculator have an important role in helping physicians decide whom to treat for primary prevention of cardiovascular disease. Physicians should consider applying the new guidelines, while having an informed consent discussion with their patients about the risks and benefits of treatment.

—Jason P. Block, MD, MPH

References

1. Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013 Nov 7 [Epub ahead of print].

2. Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. J Am Coll Cardiol 2004;44:720–32.

3. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002;106:3143–421.

4. Goff DC, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013 Nov 7 [Epub ahead of print].

5. Kolata G. Risk calculator for cholesterol appears flawed. New York Times. 17 November 2013. Accessed at www.nytimes.com/2013/11/18/health/risk-calculator-for-cholesterol-appears-flawed.html?_r_0 on 10 April 2014.

6. Ridker PM, Cook NR. Statins: new American guidelines for prevention of cardiovascular disease. Lancet 2013;382: 1762–5.

7. Downs J, Good C. New cholesterol guidelines: has Godot finally arrived? Ann Intern Med 2014;160:354–5.

Pencina MJ, Navar-Boggan AM, D’Agostino RB, et al. Application of new cholesterol guidelines to a population-based sample. N Engl J Med 2014;370:1422–31.
 

Study Overview

Objective. To quantify how many people would qualify for statin treatment under the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines [1].

Design. Descriptive, repeated cross-sectional study examining data from the 2005–2010 National Health and Nutrition Examination Surveys (NHANES). Data on the medical diagnoses and risk factors for cardiovascular disease for NHANES participants aged 40–75 years (n = 3773) were used to extrapolate to 115.4 million US adults in the same age-range. Exclusions were for triglyceride levels > 400 mg/dL (100 participants) and missing LDL cholesterol measurement (36 participants).

Main outcome measure. Percentage of the US adult population that would be recommended statin therapy according to the 2013 ACC/AHA guidelines as compared with the 2004 guideline produced by the Third Adult Treatment Panel (ATP III) of the National Cholesterol Education Program [2,3].

Main results. Of the NHANES participants, 49% were male, 13% had cardiovascular disease, 46% had hypertension, 21% had diabetes, 21% were smokers, and 41% had obesity. Median age was 56 years (interquartile range [IQR], 41–73), median total cholesterol was 199 mg/dL (IQR, 138–272), median LDL cholesterol was 118 mg/dL (IQR, 64–182), and HDL cholesterol was 52 mg/dL (IQR, 33–86).

Overall, 2135 participants (57%) qualified for statin treatment according to the ACC/AHA guidelines as compared with 1583 (42%) under the ATP III guidelines. Additional participants qualifying under the ACC/AHA guideline were more likely to be male, older in age, have a lower LDL cholesterol, and without known cardiovascular disease, diabetes, obesity, or hypertension. Extrapolated to the US population, 56 million people (49% of the US population age 40 to 75 years, 95% CI, 46–51) would be recommended for statin treatment under the ACC/AHA guidelines compared with 43.2 million (37.5%, 95% CI, 35.3–39.7) under ATP III.

Most new candidates for statins meet criteria for primary prevention of a cardiovascular event: 2.2 million persons with diabetes and 8.2 million considered at high risk for an event in 10 years based on the new ACC/AHA risk calculator [4]. Age also was an important predictor of newly eligible statin candidates. According to ATP III, 48% of 60- to 75-year-olds would qualify for treatment, but 78% would qualify based on ACC/AHA. According to extrapolated NHANES data, 25.2 million people were taking statins from 2005 to 2010; the ACC/AHA guidelines would more than double this number.

Conclusion. The 2013 ACC/AHA cholesterol treatment guidelines would substantially increase the number of patients recommended for statin therapy.

Commentary

In November 2013, the long-awaited cholesterol treatment guidelines from the ACC/AHA hit like an earthquake [5]. The guidelines called for abandoning the traditional treat-to-target approach, in which clinicians treat patients to specific levels of LDL cholesterol [1] and instead called for statin treatment based on cardiovascular risk profile. The guideline authors made this change because of the lack of evidence supporting a treat-to-target approach; nearly all randomized controlled trials with statins used fixed doses of statins rather than trying to achieve specific LDL levels. This study by Pencina and colleagues demonstrates how implementation of the new guideline could dramatically change practice. If fully implemented, the guideline would lead to treatment for more than 12 million more patients and double the number of currently treated patients. Nearly all of the newly treated patients would receive treatment for primary prevention.

The guideline defines 4 categories of patients to be considered for treatment: (1) patients with known cardiovascular disease, (2) patients with LDL cholesterol ≥ 190 mg/dL, (3) patients with diabetes aged 40 to 75 years and LDL cholesterol ≥ 70 mg/dL, and (4) patients aged 40 to 75 years with LDL cholesterol ≥ 70 mg/dL and an estimated 10-year risk of a cardiovascular event of ≥ 7.5%. The guidelines call for patients in groups 1 and 2 to receive high-intensity statins (rosuvastatin 20 to 40 mg, atorvastatin 40 to 80 mg), although patients with known cardiovascular disease > 75 years of age can receive moderate-intensity statins. Group 3 should receive high-intensity statins if their 10-year risk is ≥ 7.5%; if otherwise, they can receive a moderate-intensity statin. Group 4 should receive a moderate-to high-intensity statin. As with most guidelines, the guidelines offer the caveat that physicians should take an informed consent approach regarding treatment and make decisions in consultation with their patients.

The publicity surrounding the new guidelines was heightened by the controversy that emerged regarding the new Pooled Cohort Risk Equation developed by the guideline committee [4] for determining 10-year risk. Using data from 5 well-known cohort studies (over 24,000 participants), they created the new risk calculator because of what they viewed as limitations of existing risk calculators: (1) the lack of racial diversity in samples used to derive them, (2) the lack of use of stroke as a cardiovascular outcome, and (3) the use of some subjective outcomes, such as coronary revascularization, angina, and congestive heart failure. Critics have suggested that the new risk calculator is poorly calibrated to more recent cohorts and that the threshold for treatment (≥ 7.5% 10-year risk) is too low and should be 10% or higher [6,7].

Physicians have long used risk calculators to help guide treatment. As an example, the Framingham Heart Study risk score was endorsed by the ATP III guideline. However, all risk scores have limitations, as clearly articulated by the developers of the ACC/AHA risk calculator:

This process is admittedly imperfect; no one has 10% or 20% of a heart attack during a 10-year period. Individuals with the same estimated risk will either have or not have the event of interest, and only those patients who are destined to have an event can have their event prevented by therapy. The criticism of the risk estimation approach to treatment-decision making also applies to the alternative, and much less efficient approach, of checking the patient’s characteristics against numerous and complex inclusion and exclusion criteria for a potentially large number of pertinent trials [4].

No matter how well calibrated or thoughtful, all calculators will be flawed. But guidelines are meant to be just that—guides rather than a prescription for treatment.

Applications for Clinical Practice

The ACC and AHA have promised a 2014 update to their guideline, which may come with adjustments to the risk calculator. Perhaps calibration of the calculator in newer cohorts will improve and the threshold for treatment will change. In the meantime, the guidelines and the accompanying calculator have an important role in helping physicians decide whom to treat for primary prevention of cardiovascular disease. Physicians should consider applying the new guidelines, while having an informed consent discussion with their patients about the risks and benefits of treatment.

—Jason P. Block, MD, MPH

References

1. Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013 Nov 7 [Epub ahead of print].

2. Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. J Am Coll Cardiol 2004;44:720–32.

3. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002;106:3143–421.

4. Goff DC, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013 Nov 7 [Epub ahead of print].

5. Kolata G. Risk calculator for cholesterol appears flawed. New York Times. 17 November 2013. Accessed at www.nytimes.com/2013/11/18/health/risk-calculator-for-cholesterol-appears-flawed.html?_r_0 on 10 April 2014.

6. Ridker PM, Cook NR. Statins: new American guidelines for prevention of cardiovascular disease. Lancet 2013;382: 1762–5.

7. Downs J, Good C. New cholesterol guidelines: has Godot finally arrived? Ann Intern Med 2014;160:354–5.