Skip to main content
Log in

Adjunctive interventions in myocardial infarction: The role of statin therapy

  • Published:
Current Atherosclerosis Reports Aims and scope Submit manuscript

Abstract

Statin therapy has reduced cardiovascular morbidity and mortality across the spectrum of atherosclerosis. The administration of statins has been demonstrated to be effective in primary and secondary prevention clinical trials evaluating patients with high and low risk-factor profiles. The presumed mechanism of benefit of hypolipidemic therapy in the prevention of atherosclerotic disease was a reduction in the deposition of atherogenic lipoproteins in vulnerable areas of the coronary vasculature. Subsequent experimental studies with statins demonstrated a variety of potentially beneficial effects that would extend clinical benefit beyond lipid-lowering per se. Statin therapy beneficially alters inflammation, coagulation and fibrinolytic parameters, endothelial function, vasoreactivity, and platelet function. The demonstration of the non-lipid or pleiotropic effects provided the theoretical basis for a possible role as an adjunctive therapy in acute coronary syndromes. Retrospective analysis of a variety of early trials indicated a potential benefit of statins during acute ischemic syndromes. Recent clinical trials have addressed this important clinical question in a prospective controlled manner. The Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) and the Thrombolysis In Myocardial Infarction (TIMI)-22 studies present strong clinical evidence in favor of the administration of statins as adjunctive therapy in acute ischemic syndromes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Davidson MH, Robinson JG: Lipid-lowering effects of statins: a comparative review. Expert Opin Pharmacother 2006, 7:1701–1714.

    Article  PubMed  CAS  Google Scholar 

  2. Gossl M, Versari D, Hildebrandt H, et al.: Vulnerable plaque: detection and management. Med Clin North Am 2007, 91:573–601; ix–x.

    Article  PubMed  Google Scholar 

  3. Renault MA, Losordo DW: The matrix revolutions: matrix metalloproteinase, vasculogenesis, and ischemic tissue repair. Circ Res 2007, 100:749–750.

    Article  PubMed  CAS  Google Scholar 

  4. Libby P. Atherosclerosis: disease biology affecting the coronary vasculature. Am J Cardiol 2006, 98(12A):3Q–9Q.

    Article  PubMed  CAS  Google Scholar 

  5. Brueckmann M, Bertsch T, Lang S, et al.: Time course of systemic markers of inflammation in patients presenting with acute coronary syndromes. Clin Chem Lab Med 2004, 42:1132–1139.

    Article  PubMed  CAS  Google Scholar 

  6. Albert MA, Ridker PM: The role of C-reactive protein in cardiovascular disease risk. Curr Cardiol Rep 1999, 1:99–104.

    Article  PubMed  CAS  Google Scholar 

  7. Devaraj S, Du Clos TW, Jialal I: Binding and internalization of C-reactive protein by Fcgamma receptors on human aortic endothelial cells mediates biological effects. Arterioscler Thromb Vasc Biol 2005, 25:1359–1363.

    Article  PubMed  CAS  Google Scholar 

  8. Verma S, Wang CH, Li SH, et al.: A self-fulfilling prophecy: C-reactive protein attenuates nitric oxide production and inhibits angiogenesis. Circulation 2002, 106:913–919.

    Article  PubMed  CAS  Google Scholar 

  9. Tilley R, Mackman N: Tissue factor in hemostasis and thrombosis. Semin Thromb Hemost 2006, 32:5–10.

    Article  PubMed  CAS  Google Scholar 

  10. Asselbergs FW, Williams SM, Hebert PR, et al.: Genderspecific correlations of plasminogen activator inhibitor-1 and tissue plasminogen activator levels with cardiovascular disease-related traits. J Thromb Haemost 2007, 5:313–320.

    Article  PubMed  CAS  Google Scholar 

  11. Liao JK, Laufs U: Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol 2005, 45:89–118.

    Article  PubMed  CAS  Google Scholar 

  12. Crisby M, Nordin-Fredriksson G, Shah PK, et al.: Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques: implications for plaque stabilization. Circulation 2001, 103:926–933.

    PubMed  CAS  Google Scholar 

  13. Ridker PM: High-sensitivity C-reactive protein, inflammation, and cardiovascular risk: from concept to clinical practice to clinical benefit. Am Heart J 2004, 148(Suppl 1):S19–S26.

    Article  PubMed  CAS  Google Scholar 

  14. Inoue I, Goto S, Mizotani K, et al.: Lipophilic HMG-CoA reductase inhibitor has an anti-inflammatory effect: reduction of MRNA levels for interleukin-1beta, interleukin-6, cyclooxygenase-2, and p22phox by regulation of peroxisome proliferator-activated receptor alpha (PPARalpha) in primary endothelial cells. Life Sci 2000, 67:863–876.

    Article  PubMed  CAS  Google Scholar 

  15. Schonbeck U, Libby P: CD40 signaling and plaque instability. Circ Res 2001, 89:1092–1103.

    Article  PubMed  CAS  Google Scholar 

  16. Waehre T, Yndestad A, Smith C, et al.: Increased expression of interleukin-1 in coronary artery disease with downregulatory effects of HMG-CoA reductase inhibitors. Circulation 2004, 109:1966–1972.

    Article  PubMed  CAS  Google Scholar 

  17. Kavsak PA, MacRae AR, Newman AM, et al.: Elevated C-reactive protein in acute coronary syndrome presentation is an independent predictor of long-term mortality and heart failure. Clin Biochem 2007, 40(5–6):326–329.

    Article  PubMed  CAS  Google Scholar 

  18. Devaraj S, Rogers J, Jialal I: Statins and biomarkers of inflammation. Curr Atheroscler Rep 2007, 9:33–41.

    Article  PubMed  CAS  Google Scholar 

  19. Greenwood J, Mason JC: Statins and the vascular endothelial inflammatory response. Trends Immunol 2007, 28:88–98.

    Article  PubMed  CAS  Google Scholar 

  20. Fichtlscherer S, Rosenberger G, Walter DH, et al.: Elevated C-reactive protein levels and impaired endothelial vasoreactivity in patients with coronary artery disease. Circulation 2000, 102:1000–1006.

    PubMed  CAS  Google Scholar 

  21. Karatzis EN, Ikonomidis I, Vamvakou GD, et al.: Long-term prognostic role of flow-mediated dilatation of the brachial artery after acute coronary syndromes without ST elevation. Am J Cardiol 2006, 98:1424–1428.

    Article  PubMed  Google Scholar 

  22. Wassmann S, Ribaudo N, Faul A, et al.: Effect of atorvastatin 80 mg on endothelial cell function (forearm blood flow) in patients with pretreatment serum low-density lipoprotein cholesterol levels <130 mg/dl. Am J Cardiol 2004, 93:84–88.

    Article  PubMed  CAS  Google Scholar 

  23. Hill JM, Zalos G, Halcox JP, et al.: Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 2003, 348:593–600.

    Article  PubMed  Google Scholar 

  24. Undas A, Celinska-Lowenhoff M, Kaczor M, Musial J: New nonlipid effects of statins and their clinical relevance in cardiovascular disease. Thromb Haemost 2004, 91:1065–1077.

    PubMed  CAS  Google Scholar 

  25. Krysiak R, Okopien B, Herman Z: Effects of HMG-CoA reductase inhibitors on coagulation and fibrinolysis processes. Drugs 2003, 63:1821–1854.

    Article  PubMed  CAS  Google Scholar 

  26. Spencer FA, Fonarow GC, Frederick PD, et al.: Early withdrawal of statin therapy in patients with non-ST-segment elevation myocardial infarction: National Registry of Myocardial Infarction. Arch Intern Med 2004, 164:2162–2168.

    Article  PubMed  CAS  Google Scholar 

  27. Heeschen C, Hamm CW, Laufs U, et al.: Withdrawal of statins increases event rates in patients with acute coronary syndromes. Circulation 2002, 105:1446–1452.

    Article  PubMed  CAS  Google Scholar 

  28. McGowan MP: There is no evidence for an increase in acute coronary syndromes after short-term abrupt discontinuation of statins in stable cardiac patients. Circulation 2004, 110:2333–2335.

    Article  PubMed  CAS  Google Scholar 

  29. Thompson PL, Meredith I, Amerena J, et al.: Effect of pravastatin compared with placebo initiated within 24 hours of onset of acute myocardial infarction or unstable angina: the Pravastatin in Acute Coronary Treatment (PACT) trial. Am Heart J 2004, 148:e2.

    Article  PubMed  Google Scholar 

  30. de Lemos JA, Blazing MA, Wiviott SD, et al.: Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA 2004, 292:1307–1316.

    Article  PubMed  Google Scholar 

  31. Liem AH, van Boven AJ, Veeger NJ, et al.: Effect of fluvastatin on ischaemia following acute myocardial infarction: a randomized trial. Eur Heart J 2002, 23:1931–1937.

    Article  PubMed  CAS  Google Scholar 

  32. Schwartz GG, Olsson AG, Ezekowitz MD, et al.: Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA 2001, 285:1711–1718.

    Article  PubMed  CAS  Google Scholar 

  33. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994, 344:1383–1389.

  34. Cannon CP, Braunwald E, McCabe CH, et al.: Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004, 350:1495–1504.

    Article  PubMed  CAS  Google Scholar 

  35. Sacks FM, Pfeffer MA, Moye LA, et al.: The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med 1996, 335:1001–1009.

    Article  PubMed  CAS  Google Scholar 

  36. Smith SC Jr, Allen J, Blair SN, et al.: AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: endorsed by the National Heart, Lung, and Blood Institute. Circulation 2006, 113:2363–2372.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to John A. Farmer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jones, P.H., Farmer, J.A. Adjunctive interventions in myocardial infarction: The role of statin therapy. Curr Atheroscler Rep 10, 142–148 (2008). https://doi.org/10.1007/s11883-008-0021-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11883-008-0021-3

Keywords

Navigation