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Original Research |

Optimizing Statin Treatment for Primary Prevention of Coronary Artery Disease

Rodney A. Hayward, MD; Harlan M. Krumholz, MD; Donna M. Zulman, MD; Justin W. Timbie, PhD; and Sandeep Vijan, MD, MSc
[+] Article, Author, and Disclosure Information

From University of Michigan and Veteran Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan, and Yale University and Yale-New Haven Hospital, New Haven, Connecticut.

Acknowledgment: The authors thank Hwajung Choi, PhD, for her assistance with the statistical modeling.

Grant Support: In part by the Department of Veteran Affairs Health Services Research & Development Service's Quality Enhancement Research Initiative (QUERI DIB 98-001). The Measurement Core of the Michigan Diabetes Research & Training Center (National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health [P60 DK-20572]) provided consultative support.

Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M09-1850.

Reproducible Research Statement:Study protocol, statistical code, and data set: Available from Dr. Hayward (e-mail, rhayward@umich.edu).

Corresponding Author: Rodney A. Hayward, MD, The Robert Wood Johnson Clinical Scholars Program, University of Michigan Medical School, 6312 Medical Science Building I, 1150 West Medical Center Drive, Ann Arbor, MI 48109; e-mail, rhayward@umich.edu.

Current Author Addresses: Drs. Hayward and Zulman: The Robert Wood Johnson Clinical Scholars Program, University of Michigan Medical School, 6312 Medical Science Building I, 1150 West Medical Center Drive, Ann Arbor, MI 48109.

Dr. Krumholz: Yale University School of Medicine, 1 Church Street, Suite 200, New Haven, CT 06510.

Dr. Timbie: The RAND Corporation, 1200 South Hayes Street, Arlington, VA 22202-5050.

Dr. Vijan: Veteran Affairs Health Services Research & Development Center of Excellence, VA Ann Arbor Healthcare System, PO Box 130170, Ann Arbor, MI 48113-0170.

Author Contributions: Conception and design: R.A. Hayward, S. Vijan.

Analysis and interpretation of the data: R.A. Hayward, H.M. Krumholz, D.M. Zulman, S. Vijan.

Drafting of the article: R.A. Hayward, D.M. Zulman, J.W. Timbie, S. Vijan.

Critical revision of the article for important intellectual content: R.A. Hayward, H.M. Krumholz, D.M. Zulman, J.W. Timbie, S. Vijan.

Final approval of the article: R.A. Hayward, H.M. Krumholz, D.M. Zulman, J.W. Timbie, S. Vijan.

Statistical expertise: R.A. Hayward, J.W. Timbie, S. Vijan.

Obtaining of funding: R.A. Hayward.

Administrative, technical, or logistic support: R.A. Hayward.

Collection and assembly of data: R.A. Hayward, J.W. Timbie.

Ann Intern Med. 2010;152(2):69-77. doi:10.7326/0003-4819-152-2-201001190-00004
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Background: Although treating to lipid targets (“treat to target”) is widely recommended for coronary artery disease (CAD) prevention, some have advocated administering fixed doses of statins based on a person's estimated net benefit (“tailored treatment”).

Objective: To examine how a tailored treatment approach to statin therapy compares with a treat-to-target approach.

Design: Simulated model of population-level effects of treat-to-target and tailored treatment approaches to statin therapy.

Data Sources: Statin trials from 1994 to 2009 and nationally representative CAD risk factor data.

Target Population: U.S. persons aged 30 to 75 years with no history of myocardial infarction.

Time Horizon: Lifetime effects of 5 years of treatment.

Perspective: Societal and patient.

Intervention: Tailored treatment based on a person's 5-year CAD risk (simvastatin, 40 mg, for 5% to 15% CAD risk and atorvastatin, 40 mg, for CAD risk >15%) versus treat-to-target approaches that escalate statin dose per National Cholesterol Education Program [NCEP] III guidelines (including an intensive approach that advances treatment whenever intensification is optional by NCEP III criteria).

Outcome Measures: Quality-adjusted life-years (QALYs).

Results of Base-Case Analysis: Compared with the standard NCEP III approach, the intensive NCEP III approach treated 15 million more persons and saved 570 000 more QALYs over 5 years. The tailored strategy treated a similar number of persons, as did the intensive NCEP III approach, but saved 500 000 more QALYs and treated fewer persons with high-dose statins.

Results of Sensitivity Analysis: No circumstances were found in which a treat-to-target approach was preferable to tailored treatment.

Limitation: Model assumptions were based on available clinical data, which included few persons 75 years or older.

Conclusion: A tailored treatment strategy prevents more CAD events while treating fewer persons with high-dose statins than low-density lipoprotein cholesterol–based target approaches. Results were robust, even with assumptions favoring a treat-to-target approach.

Primary Funding Source: Department of Veteran Affairs Health Services Research & Development Service's Quality Enhancement Research Initiative.


Grahic Jump Location
Figure 1.
The LDL-C–based treat-to-target and tailored treatment strategies.

CAD = coronary artery disease; CHD = coronary heart disease; LDL-C = low-density lipoprotein cholesterol; NCEP = National Cholesterol Education Program.

* Based on risk factors and CAD.

† To convert mg/dL to mmol/L, multiply values by 0.0259.

Grahic Jump Location
Grahic Jump Location
Figure 2.
Factors influencing the relative benefits of the intensive NCEP III versus the TT approaches to statin therapy.

Results are shown when key assumptions are varied in sensitivity analyses (see Appendix Table 1 for more details), demonstrating how the TT approach results in more total population benefit, greater treatment effectiveness, and fewer persons treated intensively across the range of assumptions. CV = cardiovascular; LDL-C = low-density lipoprotein cholesterol; NCEP = National Cholesterol Education Program; QALY = quality-adjusted life-year; TT = tailored treatment.

Grahic Jump Location




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Submit a Comment/Letter
Failure to differentiate between men and women in primary prevention
Posted on February 4, 2010
Theodore Eisenberg
Cornell University
Conflict of Interest: None Declared

This article's failure to distinguish between men and women is troublesome. Several meta-analyses of primary prevention statin results for women with elevated cholesterol show no statistically significant cardiac outcome benefits (1). And results for men and women statistically significantly differ (2). Some studies even suggest increased cardiovascular risk for women or for female age subgroups (1). One of the drugs emphasized in this article, atorvastatin, has no clinical trial showing cardiac benefits to women in a primary prevention context. The ASCOT trial showed increased heart attack risk to women and the CASHMERE trial, limited to post-menopausal women, showed no benefit to women in the IMT endpoint used. CASHMERE's results have not been published in a journal nor did PFizer's website alert physicians to their existence.


1. Eisenberg T, Wells MT. Statins, cholesterol, women and primary prevention: evidence-based medicine or wishful thinking? Future Cardiology 2009; 5: 1-4.

2. Eisenberg T, Wells MT. Statins and adverse cardiovascular events in moderate-risk females: a statistical and legal analysis with implications for FDA preemption claims. Journal of Empirical Legal Studies 2008; 5: 507-50.

Conflict of Interest:

None declared

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