0

The full content of Annals is available to subscribers

Subscribe/Learn More  >
Articles |

Comparing Impact and Cost-Effectiveness of Primary Prevention Strategies for Lipid-Lowering

Mark J. Pletcher, MD, MPH; Lawrence Lazar, MD; Kirsten Bibbins-Domingo, PhD, MD; Andrew Moran, MD, MPH; Nicolas Rodondi, MD, MAS; Pamela Coxson, PhD; James Lightwood, PhD; Lawrence Williams, MSc; and Lee Goldman, MD, MPH
[+] Article and Author Information

From the University of California, San Francisco, San Francisco, California; Columbia University, New York, New York; University of Lausanne, Lausanne, Switzerland; and Brigham and Women's Hospital, Boston, Massachusetts.


Note: Preliminary results were presented at the 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention in Orlando, Florida, 28 February–3 March 2007.

Disclaimer: The manuscript was prepared by using a limited-access data set obtained by the National Heart, Lung, and Blood Institute and does not necessarily reflect the opinions or views of the Framingham Heart Study; Framingham Offspring Study; or the National Heart, Lung, and Blood Institute.

Acknowledgment: The authors thank Dr. Stephanie Earnshaw for her help with cost inputs and Dr. David Fairley for help developing the Monte Carlo simulation program for the CHD Policy Model.

Grant Support: By the Flight Attendants' Medical Research Institute and a grant from the Swanson Family Fund to the University of California (Dr. Goldman). The Framingham Heart Study and Framingham Offspring Study are conducted and supported by the National Heart, Lung, and Blood Institute in collaboration with the Framingham Heart Study and Framingham Offspring Study investigators.

Reproducible Research Statement: The CHD Policy Model is owned by an Intellectual Property Commons, currently led by Columbia University and formerly led by the University of California and Harvard University, both of which remain part of the Commons. To guarantee the reliability and integrity of the model, collaborating investigators and their institutions become part of this Commons by agreeing to 1) help maintain and improve the model and 2) have any of their uses of the model (e.g., requests for extramural funding or potential publications) reviewed for accuracy and approval by the Commons before any dissemination. Since its establishment, the Commons has included a number of funded projects, none from for-profit entities. Several investigators, including some from outside the United States, recently joined the Commons, and new members are always welcome but rarely solicited. In all decisions, maintaining the integrity, reliability, and impartiality of the model remains the primary goal. Persons who are interested in joining the Commons and are committed to improving the model and using it for scientific purposes should contact Dr. Goldman.

Potential Financial Conflicts of Interest:Consultancies: N. Rodondi (Pfizer). Honoraria: N. Rodondi (Pfizer, AstraZeneca, Merck & Co., Schering-Plough).

Requests for Single Reprints: Mark J. Pletcher, MD, MPH, University of California, San Francisco, 185 Berry Street, Suite 5700, San Francisco, CA 94107; e-mail, mpletcher@epi.ucsf.edu.

Current Author Addresses: Dr. Pletcher: University of California, San Francisco, 185 Berry Street, Suite 5700, San Francisco, CA 94107.

Dr. Lazar: 2732 Derbyshire Road, Cleveland Heights, OH 44106.

Dr. Bibbins-Domingo: University of California, San Francisco, Box 1364, San Francisco, CA 94143.

Dr. Moran: Columbia University, 622 West 168th Street, New York, NY 10032.

Dr. Rodondi: Department of Ambulatory Care and Community Medicine, University of Lausanne, Bugnon 44, Lausanne 1011, Switzerland.

Dr. Coxson: Department of General Internal Medicine, San Francisco General Hospital, Building 10, Third Floor, 1001 Potrero Avenue, San Francisco, CA 94110.

Dr. Lightwood: Department of Clinical Pharmacology, University of California, San Francisco, 3333 California Street, Suite 420, San Francisco, CA 94118.

Dr. Williams: Partners HealthCare System, 93 Worcester Street, Suite 201, Wellesley, MA 02481.

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

Author Contributions: Conception and design: M.J. Pletcher, K. Bibbins-Domingo, A. Moran, P. Coxson, L. Goldman.

Analysis and interpretation of the data: M.J. Pletcher, L. Lazar, K. Bibbins-Domingo, N. Rodondi, P. Coxson, J. Lightwood, L. Goldman.

Drafting of the article: M.J. Pletcher, P. Coxson.

Critical revision of the article for important intellectual content: M.J. Pletcher, K. Bibbins-Domingo, A. Moran, N. Rodondi, P. Coxson, L. Goldman.

Final approval of the article: M.J. Pletcher, A. Moran, N. Rodondi, P. Coxson, J. Lightwood, L. Goldman.

Statistical expertise: N. Rodondi, L. Williams.

Obtaining of funding: L. Goldman.

Administrative, technical, or logistic support: K. Bibbins-Domingo, L. Goldman.

Collection and assembly of data: M.J. Pletcher, L. Lazar, L. Williams.


Ann Intern Med. 2009;150(4):243-254. doi:10.7326/0003-4819-150-4-200902170-00005
Text Size: A A A

Background: Lipid-lowering therapy is costly but effective at reducing coronary heart disease (CHD) risk.

Objective: To assess the cost-effectiveness and public health impact of Adult Treatment Panel III (ATP III) guidelines and compare with a range of risk- and age-based alternative strategies.

Design: The CHD Policy Model, a Markov-type cost-effectiveness model.

Data Sources: National surveys (1999 to 2004), vital statistics (2000), the Framingham Heart Study (1948 to 2000), other published data, and a direct survey of statin costs (2008).

Target Population: U.S. population age 35 to 85 years.

Time Horizon: 2010 to 2040.

Perspective: Health care system.

Intervention: Lowering of low-density lipoprotein cholesterol with HMG-CoA reductase inhibitors (statins).

Outcome Measure: Incremental cost-effectiveness.

Results of Base-Case Analysis: Full adherence to ATP III primary prevention guidelines would require starting (9.7 million) or intensifying (1.4 million) statin therapy for 11.1 million adults and would prevent 20 000 myocardial infarctions and 10 000 CHD deaths per year at an annual net cost of $3.6 billion ($42 000/QALY) if low-intensity statins cost $2.11 per pill. The ATP III guidelines would be preferred over alternative strategies if society is willing to pay $50 000/QALY and statins cost $1.54 to $2.21 per pill. At higher statin costs, ATP III is not cost-effective; at lower costs, more liberal statin-prescribing strategies would be preferred; and at costs less than $0.10 per pill, treating all persons with low-density lipoprotein cholesterol levels greater than 3.4 mmol/L (>130 mg/dL) would yield net cost savings.

Results of Sensitivity Analysis: Results are sensitive to the assumptions that LDL cholesterol becomes less important as a risk factor with increasing age and that little disutility results from taking a pill every day.

Limitation: Randomized trial evidence for statin effectiveness is not available for all subgroups.

Conclusion: The ATP III guidelines are relatively cost-effective and would have a large public health impact if implemented fully in the United States. Alternate strategies may be preferred, however, depending on the cost of statins and how much society is willing to pay for better health outcomes.

Funding: Flight Attendants' Medical Research Institute and the Swanson Family Fund. The Framingham Heart Study and Framingham Offspring Study are conducted and supported by the National Heart, Lung, and Blood Institute.

Figures

Grahic Jump Location
Figure 1.
Monte Carlo analysis comparing ATP III with baseline.

We ran 1000 Monte Carlo probabilistic simulations that sampled from likely distributions for event-rate β-coefficients and other assumptions in Table 1. ATP III = Adult Treatment Panel III (4); ICER = incremental cost-effectiveness ratio; QALY = quality-adjusted life-year. Top. Incremental costs versus incremental effectiveness. The lines represent willingness-to-pay thresholds; the proportions of dots below these lines identify the likelihood that the Monte Carlo simulation results would yield an ICER below $50 000/QALY or below $100 000/QALY. Bottom. Cost-effectiveness acceptability curve. The probability of preferring ATP III over baseline is 76% at a willingness-to-pay threshold of $50 000/QALY and 100% at $100 000/QALY.

Grahic Jump Location
Grahic Jump Location
Figure 2.
Expected costs and utilities associated with cholesterol-lowering strategies.

Strategies connected by a line dominate the other strategies, either directly or by extension. Dominated strategies are both less effective and more costly when compared with a particular dominating strategy (direct) or some mixture of the dominating strategies (by extension). Incremental cost-effectiveness ratios for numbered line segments are: 1) $37 000/QALY; 2) $46 000/QALY; 3) $72 000/QALY; 4) $151 000/QALY; and 5) $201 000/QALY. Risk >X% and age >X are strategies that recommend treatment for all persons with low-density lipoprotein cholesterol levels greater than 3.4 mmol/L (>130 mg/dL) when the estimated 10-year coronary heart disease risk (risk-based) or age (age-based) is greater than a given threshold X. “Age >55M/65W” is a strategy that uses an age threshold of 55 years for men and 65 years for women. ATP III = Adult Treatment Panel III (4); QALY = quality-adjusted life-year.

Grahic Jump Location
Grahic Jump Location
Figure 3.
Monte Carlo analysis comparing the risk-greater-than-10% strategy with ATP III.

We ran 1000 Monte Carlo probabilistic simulations that sampled from likely distributions for event-rate β-coefficients and other assumptions in Table 1. The risk-greater-than-10% strategy recommends treatment for all persons with low-density lipoprotein cholesterol levels greater than 3.4 mmol/L (>130 mg/dL) and an estimated 10-year coronary heart disease risk greater than 10%. ATP III = Adult Treatment Panel III (4); ICER = incremental cost-effectiveness ratio; QALY = quality-adjusted life-year. Top. Incremental costs versus incremental effectiveness. The lines represent willingness-to-pay thresholds; the proportions of dots below these lines identify the likelihood that the Monte Carlo simulation results would yield an ICER below $50 000/QALY or below $100 000/QALY. Bottom. Cost-effectiveness acceptability curve. The probability of preferring the risk-greater-than-10% strategy over ATP III is 0% at a willingness-to-pay threshold of $50 000/QALY and 1% at $100 000/QALY.

Grahic Jump Location
Grahic Jump Location
Appendix Figure 1.
Expected costs and utilities associated with cholesterol-lowering strategies.

Alternate scenario of Figure 2 showing when the low-density lipoprotein cholesterol coefficient is set to 0.0092. ATP III = Adult Treatment Panel III (4); QALY = quality-adjusted life-year.

Grahic Jump Location
Grahic Jump Location
Appendix Figure 2.
Monte Carlo analysis comparing the risk-greater-than-10% strategy with ATP III.

Alternate scenario of Figure 3 showing when the low-density lipoprotein cholesterol coefficient is set to 0.0092. ATP III = Adult Treatment Panel III (4); ICER = incremental cost-effectiveness ratio; QALY = quality-adjusted life-year.

Grahic Jump Location

Tables

References

Letters

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Comments

Submit a Comment
Submit a Comment

Summary for Patients

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.

Toolkit

Buy Now

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Advertisement
Related Articles
Related Point of Care
Topic Collections
PubMed Articles
Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.
(Required)
(Required)