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Statins for Secondary Prevention of Cardiovascular Disease: The Right Dose

Spector R.a · Snapinn S.M.b

Author affiliations

aRobert Wood Johnson Medical School, Piscataway, N.J., and bGlobal Biostatistics and Epidemiology, Amgen, Inc., Thousand Oaks, Calif., USA

Corresponding Author

Reynold Spector, MD

105 Stone Hill Road

Colts Neck, NJ 07722 (USA)

Tel./Fax +1 732 780 5762

E-Mail mspec007@verizon.net

Related Articles for ""

Pharmacology 2011;87:63–69

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Since the publication of the 4S trial in 1994, there has emerged a consensus that statins save lives and decrease myocardial infarctions and strokes in coronary artery disease (CAD) patients irrespective of baseline serum cholesterol. However, there is controversy over the correct dose and the utility of the treatment-to-goal (cholesterol, low-density lipoprotein) approach. To answer remaining questions about the optimal statin dose in CAD patients, we have performed simple and meta-analyses of 3 large long-term (approx. 5 years) dose-clinical response studies (TNT, IDEAL, and SEARCH) and compared the results with older data including long-term safety data. The results show that raising the dose of simvastatin or atorvastatin to 80 mg confers no mortality advantage, an increase in adverse reactions and only a slight decrease in myocardial infarctions and stroke versus a lower dose. These results suggest a cost-effective approach of a single safe dose (40 mg of inexpensive generic simvastatin or atorvastatin) for almost all CAD patients and makes treatment-to-goal and cholesterol monitoring (except to check for medication compliance) unnecessary; moreover, it is likely to improve the weakness in statin use – medication compliance.

© 2011 S. Karger AG, Basel


  1. The Scandinavian Simvastatin Survival Study Group: Randomised trial of cholesterol lowering in 4,444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383–1389.
  2. The LIPID Study Group: Long-term effectiveness and safety of pravastatin in 9,014 patients with coronary heart disease and average cholesterol concentrations: the LIPID trial follow-up. Lancet 2002;359:1379–1387.
  3. Heart Protection Study Collaborative Group: MRC/BHF heart protection study of cholesterol lowering with simvastatin in 20,536 high-risk individuals; a randomised placebo-controlled trial. Lancet 2002;360:7–22.
  4. Sacks FM, Tonkin AM, Shepherd J, et al: Effect of pravastatin on coronary disease events in subgroups defined by coronary risk factors: the prospective pravastatin pooling project. Circulation 2000;102:1893–1900.
  5. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: 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 III). JAMA 2001;285:2486–2497.
  6. Grundy SM, Cleeman JI, Merz CNB, et al: Implications of recent clinical trials for the national cholesterol education program adult treatment panel III guidelines. Circulation 2004;110:227–239.
  7. Shepherd J: Resource management in prevention of coronary heart disease: optimizing prescription of lipid-lowering drugs. Lancet 2002;359:2271–2273.
  8. Donner-Banzhoff N, Sönnichsen A: Strategies for prescribing statins. Evidence supports prescribing a standard dose without further testing or dose adjustment. BMJ 2008;336:288–289.
  9. Hayward RA, Hofer TP, Vijan S: Narrative review: lack of evidence for recommended low-density lipoprotein treatment targets: a solvable problem. Ann Intern Med 2006;145:520–530.
  10. Hayward RA, Krumholz HM, Zulman DM, Timbie JW, Vijan S: Optimizing statin treatment for primary prevention of coronary artery disease. Ann Intern Med 2010;152:69–77.
  11. Spector R: The Scientific Basis of Clinical Pharmacology: Principles and Examples. Boston, Little, Brown and Co, 1986.
  12. LaRosa JC, Grundy SM, Waters DD, et al: Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005;352:1425–1435.
  13. Pedersen TR, Faergeman O, Kastelein JJP, et al: High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction. The IDEAL Study: a randomized controlled trial. JAMA 2005;294:2437–2445.
  14. SEARCH Study Collaborative Group Oxford: Study of the effectiveness of additional reductions in cholesterol and homocysteine (SEARCH): characteristics of a randomized trial among 12,064 myocardial infarction survivors. Am Heart J 2007;154:815–823.
  15. SEARCH Collaborative Group: Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomized trial. Lancet 2010;376: 1658–1669.
  16. Boden WE, O’Rourke RA, Teo KK, et al: Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med 2007;356:1503–1516.
  17. Tonino PA, De Bruyne B, Pijls NH, et al: Fractional flow reserve versus angiograph for guiding percutaneous coronary intervention. N Engl J Med 2009;360:213–224.
  18. Mahmarian JJ, Dakik HA, Filipchuk NG, et al: An initial strategy of intensive medical therapy is comparable to that of coronary revascularization for suppression of scintigraphic ischemia in high-risk but stable survivors of acute myocardial infarction. J Am Coll Cardiol 2006;48:2458–2467.
  19. Freund JE: Modern Elementary Statistics, ed 3. Englewood Cliffs, Prentice-Hall, 1967, pp 285–287.
  20. Kulinskaya E, Morgenthaler S, Staudte RG: Meta-Analysis: A Guide to Calibrating and Combining Statistical Evidence. Chichester, Wiley, 2008.
  21. Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR: Practical methods for incorporating summary time-to-event data into meta-analysis. Trials 2007;8:16.
  22. Physicians’ Desk Reference 2010. Atorvastatin. Montvale, PDR Network, 2010, pp 2504–2507.
  23. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators: High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006;355:549–559.
  24. The SEARCH Study Collaborative Group: SLC 0131 variants and statin-induced myopathy – A genome wide study. N Engl J Med 2008;359:789–799.
  25. Bates TR, Connaughton VM, Watts GF: Non-adherence to statin therapy: a major challenge for preventive cardiology. Expert Opin Pharmacother 2009;10:2973–2985.
  26. Shroufi A, Powles JW: Adherence and chemoprevention in major cardiovascular disease: a simulation study of the benefits of additional use of statins. J Epidemiol Community Health 2010;64:109–113.
  27. Sackett DL, Haynes RB: Compliance with Therapeutic Regimens. Baltimore, Johns Hopkins University Press, 1976.
  28. Cannon CP: The IDEAL cholesterol: lower the better. JAMA 2005;294:2492–2494.

Article / Publication Details

First-Page Preview
Abstract of Review

Received: August 20, 2010
Accepted: November 19, 2010
Published online: January 11, 2011
Issue release date: February 2011

Number of Print Pages: 7
Number of Figures: 0
Number of Tables: 4

ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)

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