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Cost-Effectiveness and Population Impact of Statins for Primary Prevention in Adults Aged 75 Years or Older in the United StatesStatins for Primary Prevention in U.S. Adults Aged 75 Years or Older

Michelle C. Odden, PhD; Mark J. Pletcher, MD, MPH; Pamela G. Coxson, PhD; Divya Thekkethala, BS; David Guzman, MS; David Heller, MD; Lee Goldman, MD, MPH; and Kirsten Bibbins-Domingo, MD, PhD
[+] Article, Author, and Disclosure Information

From Oregon State University, Corvallis, Oregon; University of California, San Francisco, San Francisco, California; and Columbia University, New York, New York.

Disclaimer: Dr. Bibbins-Domingo is currently co-vice chair of the U.S. Preventive Services Task Force (USPSTF). This work does not necessarily represent the views and policies of the USPSTF. This manuscript was prepared using Framingham Cohort and Framingham Offspring Research Materials obtained from the NHLBI Biologic Specimen and Data Repository Information Coordinating Center and does not necessarily reflect the opinions or views of the Framingham Cohort, Framingham Offspring, or the NHLBI.

Grant Support: By the American Heart Association Western States Affiliate (11CRP7210088), the National Institute on Aging (K01AG039387), and the National Institute for Diabetes and Digestive and Kidney Diseases (K24DK103992).

Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-1430.

Reproducible Research Statement:Study protocol: Not available. Statistical code: Persons interested in joining the Intellectual Property Commons that is committed to improving the model and using it for scientific purposes should contact Dr. Goldman (e-mail, lgoldman@columbia.edu). Data set: All data are publicly available, and sources are listed in the references and the Appendix.

Requests for Single Reprints: Michelle C. Odden, PhD, Oregon State University, 141B Milam Hall, Corvallis, OR 97331.

Current Author Addresses: Dr. Odden and Ms. Thekkethala: Oregon State University, 141B Milam Hall, Corvallis, OR 97331.

Dr. Pletcher: Department of Epidemiology and Biostatistics, University of California, San Francisco, UCSF Box 0560, 185 Berry Street, Lobby 5, Suite 5700, San Francisco, CA 94107-1762.

Drs. Coxson, Heller, and Bibbins-Domingo and Mr. Guzman: Department of Medicine, University of California, San Francisco, 1001 Potrero Avenue, Building 10, W13, UCSF-SFGH Box 1364, San Francisco, CA 94110.

Dr. Goldman: Columbia University Medical Center, College of Physicians and Surgeons, 630 West 168th Street, 2nd Floor, Room 401, New York, NY 10032.

Author Contributions: Conception and design: M.C. Odden, K. Bibbins-Domingo.

Analysis and interpretation of the data: M.C. Odden, M.J. Pletcher, P.G. Coxson, D. Thekkethala, D. Guzman, D. Heller, L. Goldman, K. Bibbins-Domingo.

Drafting of the article: M.C. Odden, K. Bibbins-Domingo.

Critical revision of the article for important intellectual content: M.C. Odden, M.J. Pletcher, P.G. Coxson, D. Thekkethala, D. Heller, L. Goldman, K. Bibbins-Domingo.

Final approval of the article: M.C. Odden, M.J. Pletcher, D. Heller, L. Goldman, K. Bibbins-Domingo.

Provision of study materials or patients: L. Goldman, K. Bibbins-Domingo.

Statistical expertise: M.C. Odden, P.G. Coxson, K. Bibbins-Domingo.

Obtaining of funding: M.C. Odden, K. Bibbins-Domingo.

Administrative, technical, or logistic support: M.C. Odden, D. Thekkethala, L. Goldman, K. Bibbins-Domingo.

Collection and assembly of data: M.C. Odden, D. Thekkethala, D. Guzman, K. Bibbins-Domingo.

Ann Intern Med. 2015;162(8):533-541. doi:10.7326/M14-1430
Text Size: A A A

Background: Evidence to guide primary prevention in adults aged 75 years or older is limited.

Objective: To project the population impact and cost-effectiveness of statin therapy in adults aged 75 years or older.

Design: Forecasting study using the Cardiovascular Disease Policy Model, a Markov model.

Data Sources: Trial, cohort, and nationally representative data sources.

Target Population: U.S. adults aged 75 to 94 years.

Time Horizon: 10 years.

Perspective: Health care system.

Intervention: Statins for primary prevention based on low-density lipoprotein cholesterol threshold of 4.91 mmol/L (190 mg/dL), 4.14 mmol/L (160 mg/dL), or 3.36 mmol/L (130 mg/dL); presence of diabetes; or 10-year risk score of at least 7.5%.

Outcome Measures: Myocardial infarction (MI), coronary heart disease (CHD) death, disability-adjusted life-years, and costs.

Results of Base-Case Analysis: All adults aged 75 years or older in the National Health and Nutrition Examination Survey have a 10-year risk score greater than 7.5%. If statins had no effect on functional limitation or cognitive impairment, all primary prevention strategies would prevent MIs and CHD deaths and be cost-effective. Treatment of all adults aged 75 to 94 years would result in 8 million additional users and prevent 105 000 (4.3%) incident MIs and 68 000 (2.3%) CHD deaths at an incremental cost per disability-adjusted life-year of $25 200.

Results of Sensitivity Analysis: An increased relative risk for functional limitation or mild cognitive impairment of 1.10 to 1.29 could offset the cardiovascular benefits.

Limitation: Limited trial evidence targeting primary prevention in adults aged 75 years or older.

Conclusion: At effectiveness similar to that in trials, statins are projected to be cost-effective for primary prevention; however, even a small increase in geriatric-specific adverse effects could offset the cardiovascular benefit. Improved data on the potential benefits and harms of statins are needed to inform decision making.

Primary Funding Source: American Heart Association Western States Affiliate, National Institute on Aging, and the National Institute for Diabetes on Digestive and Kidney Diseases.


Grahic Jump Location

Sensitivity analysis of magnitude of statin-associated DALY reduction needed to offset cardiovascular benefit.

The value of the statin-associated DALY reduction at which the lines cross the x-axis is the magnitude needed to offset the cardiovascular benefit and result in no net DALYs gained. DALY = disability-adjusted life-year; LDL-C = low-density lipoprotein cholesterol.

Grahic Jump Location
Grahic Jump Location
Appendix Figure.

Cardiovascular Disease Policy Model structure and disease states.

BMI = body mass index; CHD = coronary heart disease; CVD = cardiovascular disease; HDL = high-density lipoprotein; LDL = low-density lipoprotein; MI = myocardial infarction.

Grahic Jump Location




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Submit a Comment/Letter
Posted on April 23, 2015
Jennifer G Robinson, MD, MPH
University of Iowa
Conflict of Interest: None Declared
The paper by Odden, et al did not include stroke in their estimate of the cost-effectiveness of statins for primary prevention in individuals 75 and older. This results in an underestimate of the benefits of statins in this age group, and an overestimate of the costs. Stroke increases dramatically with advancing age, and comprised a large proportion of cardiovascular events in this age group. Statins reduce the risk of ischemic stroke similar to the reduction in CHD risk. The costs of nonfatal strokes are high, including prolonged hospitalization and long term care costs that are not present for CHD.

In addition the authors misrepresent the inclusiveness of their analysis by referring repeatedly to cardiovascular disease reduction, and failing to mention the lack of the inclusion of stroke as a serious limitation. The term cardiovascular disease includes stroke as well as CHD.

While it is encouraging that statins for the primary prevention of CHD after age 75 are cost-effective at $25,200 per disability adjusted life year, the full potential for cost-effectiveness, or potentially cost-savings, cannot be evaluated without considering the full benefits of statins for preventing both stroke and CHD.
Improving the ASCVD risk calculation and primary prevention
Posted on April 30, 2015
Marcus M. Reidenberg, MD
Weill Cornell Medical College
Conflict of Interest: None Declared
The ACC/AHA 2013 guidelines (1) state that everyone with an ASCVD event risk >7.5% per 10 years should take statins. This would include nearly everyone older than 70. Olden, et al, state this threshold doesn’t separate high from low risk patients and added LDL levels for this purpose (2). The guidelines include diet, smoking, exercise, and weight as important risk factors. Modest alcohol consumption also lowers risk (3). A Mediterranean diet alone reduced the ASCVD rate by 27% compared to an ordinary (control) diet (4). Akesson, et al, found that people with the best modifiable lifestyle factors had only 14% of the myocardial infarctions of people with the worst (3).
If Odden, et al, stratified their subjects by alcohol intake, diet, and physical activity as well as by family history (5,6), those with better lifestyles and good family histories would have less absolute benefit from statins than the average and those with worse would have more. A discussion individualized for a patient about ASCVD risk reduction requires knowledge of the likely risk reduction for a specific patient based on all the lifestyle factors of Akesson (3) and family history in addition to the factors in the current risk calculator (http://tools.cardiosource.org/ASCVD-Risk-Estimator/ ). One should not focus on statins and neglect change in modifiable lifestyle factors because they can make such a large difference in prognosis.
If these additional lifestyle factors and family history were added to the ASCVD risk calculator, a more personalized risk assessment could be made and a more relevant comprehensive discussion about primary prevention could be held.

1. ACC/AHA Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults. Circulation 2014; 129 (suppl 2): S1-S45.

2. Odden MC, Pletcher MJ, Coxson PG, et al. Cost-effectiveness and population impact of statins for primary prevention in adults aged 75years or older in the United States. Ann Intern Med. 2015; 162: 533-541

3. Akesson A, Larsson SC, Discacciati A, Wold,A. Low-risk diet and lifestyle habits in the primary prevention of myocardial infarction in men. J Amer Col Cardiology 2014; 64: 1299-1306

4. Estruch R, Ros E, Salas-Salvado J, et al. Primary prevention of cardiovascular disease with a Mediterranean diet. New Engl J Med 2013; 368: 1279-1290.

5. Leander K, Hallqvist J, Reuterwall C, Ahlbom A, de Faire U. Family history of coronary heart disease, a strong risk factor for myocardial infarction interacting with other cardiovascular risk factors. Epidemiology 2001; 12: 215-221.

6. Prabhakaran D, Jeemon P. Should your family history of coronary heart disease scare you? Mount sinai J Med 2012; 79: 721-732
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Summary for Patients

Statins for Primary Prevention in Older Adults

The full report is titled “Cost-Effectiveness and Population Impact of Statins for Primary Prevention in Adults Aged 75 Years or Older in the United States.” It is in the 21 April 2015 issue of Annals of Internal Medicine (volume 162, pages 533-541). The authors are M.C. Odden, M.J. Pletcher, P.G. Coxson, D. Thekkethala, D. Guzman, D. Heller, L. Goldman, and K. Bibbins-Domingo.


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