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Aspirin, Statins, or Both Drugs for the Primary Prevention of Coronary Heart Disease Events in Men: A Cost–Utility Analysis

Michael Pignone, MD, MPH; Stephanie Earnshaw, PhD; Jeffrey A. Tice, MD; and Mark J. Pletcher, MD, MPH
[+] Article and Author Information

From University of North Carolina and RTI–University of North Carolina Center for Health Promotion Economics, Chapel Hill, North Carolina; RTI Health Solutions, Research Triangle Park, North Carolina; and University of California, San Francisco, California.


Acknowledgments: The authors thank Evan Sloan for his assistance in preparation of the manuscript and Sumeet Patil and Chris Graham for their assistance with developing the figures and tables.

Grant Support: By Bayer (Dr. Pignone) and by grant number 1P30CD000138-01 from the Centers for Disease Control and Prevention (Dr. Pignone).

Potential Financial Conflicts of Interest: Consultancies: M. Pignone (Bayer, Pfizer Inc.); Honoraria: M. Pignone (Bayer, Pfizer Inc.); Expert testimony: M. Pignone (Bayer); Grants received: M. Pignone (Bayer), S. Earnshaw (Bayer); Other: M. Pignone (Bayer).

Requests for Single Reprints: Michael Pignone, MD, MPH, University of North Carolina Division of General Internal Medicine, 5039 Old Clinic Building, UNC Hospital, Chapel Hill, NC 27599-7110; e-mail, pignone@med.unc.edu.

Current Author Addresses: Dr. Pignone: University of North Carolina Division of General Internal Medicine, 5039 Old Clinic Building, UNC Hospital, Chapel Hill, NC 27599-7110.

Dr. Earnshaw: RTI Health Solutions, P.O. Box 12194, Research Triangle Park, NC 27709.

Dr. Tice: Department of Medicine, University of California, San Francisco, 1701 Divisadero Street, San Francisco, CA 94143-1732.

Dr. Pletcher: Department of Epidemiology and Biostatistics, University of California, San Francisco, 185 Berry Street, Lobby 4, Suite 5700, San Francisco, CA 94107.

Author Contributions: Conception and design: M. Pignone, S. Earnshaw, J.A. Tice, M.J. Pletcher.

Analysis and interpretation of the data: M. Pignone, S. Earnshaw, J.A. Tice, M.J. Pletcher.

Drafting of the article: M. Pignone, S. Earnshaw.

Critical revision of the article for important intellectual content: M. Pignone, S. Earnshaw, J.A. Tice, M.J. Pletcher.

Final approval of the article: M. Pignone, S. Earnshaw, J.A. Tice, M.J. Pletcher.

Provision of study materials or patients: S. Earnshaw.

Statistical expertise: S. Earnshaw, M.J. Pletcher.

Administrative, technical, or logistic support: M. Pignone, S. Earnshaw.

Collection and assembly of data: S. Earnshaw.


Ann Intern Med. 2006;144(5):326-336. doi:10.7326/0003-4819-144-5-200603070-00007
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To examine the cost and utility associated with aspirin and with statin use, we used Microsoft Excel 2002 for Windows (Microsoft Corp., Redmond, Washington) to develop a Markov state-transition model. The model was designed to simulate cohorts of initially healthy middle-aged men with no history of cardiovascular events and with various levels of 10-year risk for CHD (Figure 1).

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Figures

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Figure 1.
General structure of the Markov model.

Patients enter the model while taking their specified therapy and can progress from healthy to other states, including death, in each cycle. Patients who have aspirin-related gastrointestinal bleeding or statin-related myopathy stop taking the offending medication. Hemorrhagic stroke is modeled separately in the alternate scenario only. MI = myocardial infarction.

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Figure 2.
Effect of annual statin cost on cost-effectiveness for the combination of aspirin and a statin versus aspirin alone.

Statin cost is expressed in 2003 dollars. Base-case value is shown with the dotted vertical line.

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Figure 3.
Effect of the annual excess risk for gastrointestinal bleeding with aspirin on the cost–utility ratio for aspirin versus no treatment.

Base-case value is shown with the dotted vertical line. Cost–utility ratios below $0 per quality-adjusted life-year represent the range over which aspirin is more effective and less costly.

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Figure 4.
Results of probabilistic sensitivity analysis for men with a 10-year risk for CHD of 7.5% (base case): aspirin versus no treatment.

Plot of incremental costs versus incremental quality-adjusted life-years for aspirin versus no treatment; the diagonal line represents the incremental cost-effectiveness ratio of $50 000. Individual dots represent results for each of 1000 iterations of the model; quadrant 1 contains 1.80% of iterations, quadrant 2 contains 0.00%, quadrant 3 contains 7.20%, and quadrant 4 contains 91.00%.

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Appendix Figure 1. Plot of incremental costs versus incremental quality-adjusted life-years for aspirin versus no treatment; the diagonal line represents the incremental cost-effectiveness ratio of $50 000. Individual dots represent results for each of 1000 iterations of the model; quadrant 1 contains 69.80% of iterations, quadrant 2 contains 25.10%, quadrant 3 contains 1.20%, and quadrant 4 contains 3.90%. Cost-effectiveness acceptability curve for aspirin versus no treatment.
Results of probabilistic sensitivity analysis for men with a 10-year risk for CHD of 2.5%: aspirin versus no treatment.Top.Bottom.
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Appendix Figure 2. Plot of incremental costs versus incremental quality-adjusted life-years for aspirin versus no treatment; the diagonal line represents the incremental cost-effectiveness ratio of $50 000. Individual dots represent results for each of 1000 iterations of the model; quadrant 1 contains 32.80% of iterations, quadrant 2 contains 3.40%, quadrant 3 contains 6.50%, and quadrant 4 contains 57.30%. Cost-effectiveness acceptability curve for aspirin versus no treatment.
Results of probabilistic sensitivity analysis for men with a 10-year risk for CHD of 5%: aspirin versus no treatment.Top.Bottom.
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Appendix Figure 3. Plot of incremental costs versus incremental quality-adjusted life-years for aspirin versus no treatment; the diagonal line represents the incremental cost-effectiveness ratio of $50 000. Individual dots represent results for each of 1000 iterations of the model; quadrant 1 contains 0.3% of iterations, quadrant 2 contains 0.0%, quadrant 3 contains 4.6%, and quadrant 4 contains 95.1%.
Results of probabilistic sensitivity analysis for men with a 10-year risk for CHD of 10%: aspirin versus no treatment.
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Appendix Figure 4. Plot of incremental costs versus incremental quality-adjusted life-years for aspirin versus no treatment; the diagonal line represents the incremental cost-effectiveness ratio of $50 000. Individual dots represent results for each of 1000 iterations of the model; quadrant 1 contains 0.0% of iterations, quadrant 2 contains 0.0%, quadrant 3 contains 2.8%, and quadrant 4 contains 97.2%.
Results of probabilistic sensitivity analysis for men with a 10-year risk for CHD of 15%: aspirin versus no treatment.
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Appendix Figure 5. Plot of incremental costs versus incremental quality-adjusted life-years for aspirin versus no treatment; the diagonal line represents the incremental cost-effectiveness ratio of $50 000. Individual dots represent results for each of 1000 iterations of the model; quadrant 1 contains 0.0% of iterations, quadrant 2 contains 0.0%, quadrant 3 contains 2.8%, and quadrant 4 contains 97.2%.
Results of probabilistic sensitivity analysis for men with a 10-year risk for CHD of 25%: aspirin versus no treatment.
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Appendix Figure 6. Plot of incremental costs versus incremental quality-adjusted life-years for combination therapy with aspirin and a statin versus aspirin alone; the diagonal line represents the incremental cost-effectiveness ratio of $50 000. Individual dots represent results for each of 1000 iterations of the model; quadrant 1 contains 98.9% of iterations, quadrant 2 contains 1.1%, quadrant 3 contains 0.0%, and quadrant 4 contains 0.0%. Cost-effectiveness acceptability curve for combination therapy with aspirin and a statin versus aspirin alone.
Results of probabilistic sensitivity analysis for men with a 10-year risk for CHD of 10%: aspirin plus statin versus aspirin alone.Top.Bottom.
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Appendix Figure 7. Plot of incremental costs versus incremental quality-adjusted life-years for combination therapy with aspirin and a statin versus aspirin alone; the diagonal line represents the incremental cost-effectiveness ratio of $50 000. Individual dots represent results for each of 1000 iterations of the model; quadrant 1 contains 97% of iterations, quadrant 2 contains 3%, quadrant 3 contains 0%, and quadrant 4 contains 0%. Cost-effectiveness acceptability curve for combination therapy with aspirin and a statin versus aspirin alone.
Results of probabilistic sensitivity analysis for men with a 10-year risk for CHD of 15%: aspirin plus statin versus aspirin alone.Top.Bottom.
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Tables

References

Letters

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cost effectiveness of statins added to aspirin therapy
Posted on April 6, 2006
mark k chelmowski
Advanced Healthcare
Conflict of Interest: None Declared

Pignone, et. al. (1) concluded that adding a statin to aspirin therapy is cost effective then the CHD risk is greater than 10% (1). In their model, the authors used a yearly statin cost of $730., which was the average Red Book cost between 10mg of lovastatin and simvastatin.

I find in my clinical practice, that patients need higher doses of these drugs or more potent statins or even a second lipid lowering drug to reach the guidelines set by the NCEP panel (2). These approaches are more expensive than the model indicates. Does he author's model tell us at what 10 year CHD risk a patient would need to be to make it cost effective to use 80mg of atorvastatin, for instance?

Previous authors have questioned the cost effectiveness of statins in primary prevention for younger, lower risk patients (3). I hope that the conclusions in the article by Pignone, et al.(1) is heeded by the organizations that are trying to measure quality. Bbaseline CHD risk of patients should be considered when report cards are issued. However, in this era of looming "pay for performance" incentives, physicians may feel compelled to statin therapy in more patients and try to get all patients to certain LDL goals, regardless of their estimated 10 year risk.

references: 1. Michael Pignone, Stephanie Earnshaw, Jeffrey A. Tice, and Mark J. Pletcher Aspirin, Statins, or Both Drugs for the Primary Prevention of Coronary Heart Disease Events in Men: A Cost"“Utility Analysis Ann Intern Med 2006; 144: 326-336

2. National Cholesterol Educational Program. Executive Summary of the 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 111) JAMA. 2001;285:2486-97

3. Prosser LA, Stinnett AA, Goldman PA, Williams LW, Hunink MG, Goldman L, Weinstein MC. Related Articles, Links

Cost-effectiveness of cholesterol-lowering therapies according to selected patient characteristics. Ann Intern Med. 2000 May 16;132(10):769-79.

Conflict of Interest:

None declared

Response to letter from Dr. Chelmowski
Posted on May 10, 2006
Michael Pignone
University of North Carolina - Chapel Hill
Conflict of Interest: None Declared

To the Editor,

The effectiveness of high-dose statins or combination lipid lowering therapy for primary prevention of coronary heart disease events has not been studied to date and was not included as part of our model. The trials that formed the basis of our estimates of costs and effectiveness in CHD risk reduction employed low to medium doses of a single agent and used minimal or no adjustment based on lipid levels. (1) If more aggressive lipid lowering treatment were to be found more effective in CHD event prevention, then further analyses would need to consider whether the additional costs and potential increase in adverse effects were sufficiently off-set by the additional degree of effectiveness.

Our analysis identified a lower cost per quality adjusted life year gained than the previous analysis by Prosser and colleagues. (2) Its results are similar to those of other models that have examined the cost- effectiveness of statins for primary prevention. (3) Further studies are required to better identify reasons for the observed differences in results.(4)

I agree with Dr. Chelmowski's recommendation that baseline risk of CHD events be considered when measuring quality and developing pay for performance programs for CHD prevention. Recent efforts to develop methods to perform more informative evaluations are promising, but will require improved informatics systems to be feasible for broad application. (5)

Michael Pignone, MD, MPH Associate Professor of Medicine University of North Carolina- Chapel Hill

References:

1. Pignone M, Phillips C, Mulrow C. Use of lipid lowering drugs for primary prevention of coronary heart disease: meta-analysis of randomised trials. BMJ. 2000; 321:983-6.

2. Prosser LA, Stinnett AA, Goldman PA, Williams LW, Hunink MG, Goldman L, Weinstein MC. Cost-effectiveness of cholesterol-lowering therapies according to selected patient characteristics. Ann Intern Med. 2000; 132(10):769-79.

3. Pickin DM, McCabe CJ, Ramsay LE, Payne N, Haq IU, Yeo WW, Jackson PR. Cost effectiveness of HMG-CoA reductase inhibitor (statin) treatment related to the risk of coronary heart disease and cost of drug treatment. Heart. 1999; 82:325-32

4. Pignone M, Saha S, Hoerger T, Lohr KN, Teutsch S, Mandelblatt J.Challenges in systematic reviews of economic analyses. Ann Intern Med. 2005;142(12 Pt 2):1073-9.

5. Rodondi N, Peng T, Karter AJ, Bauer DC, Vittinghoff E, Tang S, Pettitt D, Kerr EA, Selby JV. Therapy modifications in response to poorly controlled hypertension, dyslipidemia, and diabetes mellitus. Ann Intern Med. 2006; 144(7):475-84.

Conflict of Interest:

None declared

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Summary for Patients

The Cost-Effectiveness of Aspirin, Statins, or Both Drugs in the Primary Prevention of Heart Disease

The summary below is from the full report titled “Aspirin, Statins, or Both Drugs for the Primary Prevention of Coronary Heart Disease Events in Men: A Cost–Utility Analysis.” It is in the 7 March 2006 issue of Annals of Internal Medicine (volume 144, pages 326-336). The authors are M. Pignone, S. Earnshaw, J.A. Tice, and M.J. Pletcher.

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